Pub Date : 2018-10-06Epub Date: 2018-08-10DOI: 10.1146/annurev-cellbio-100616-060600
John McCullough, Adam Frost, Wesley I Sundquist
The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.
{"title":"Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes.","authors":"John McCullough, Adam Frost, Wesley I Sundquist","doi":"10.1146/annurev-cellbio-100616-060600","DOIUrl":"10.1146/annurev-cellbio-100616-060600","url":null,"abstract":"<p><p>The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"85-109"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100616-060600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36386697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-07-20DOI: 10.1146/annurev-cellbio-100616-060553
Binyam Mogessie, Kathleen Scheffler, Melina Schuh
Fertilizable eggs develop from diploid precursor cells termed oocytes. Once every menstrual cycle, an oocyte matures into a fertilizable egg in the ovary. To this end, the oocyte eliminates half of its chromosomes into a small cell termed a polar body. The egg is then released into the Fallopian tube, where it can be fertilized. Upon fertilization, the egg completes the second meiotic division, and the mitotic division of the embryo starts. This review highlights recent work that has shed light on the cytoskeletal structures that drive the meiotic divisions of the oocyte in mammals. In particular, we focus on how mammalian oocytes assemble a microtubule spindle in the absence of centrosomes, how they position the spindle in preparation for polar body extrusion, and how the spindle segregates the chromosomes. We primarily focus on mouse oocytes as a model system but also highlight recent insights from human oocytes.
{"title":"Assembly and Positioning of the Oocyte Meiotic Spindle.","authors":"Binyam Mogessie, Kathleen Scheffler, Melina Schuh","doi":"10.1146/annurev-cellbio-100616-060553","DOIUrl":"10.1146/annurev-cellbio-100616-060553","url":null,"abstract":"<p><p>Fertilizable eggs develop from diploid precursor cells termed oocytes. Once every menstrual cycle, an oocyte matures into a fertilizable egg in the ovary. To this end, the oocyte eliminates half of its chromosomes into a small cell termed a polar body. The egg is then released into the Fallopian tube, where it can be fertilized. Upon fertilization, the egg completes the second meiotic division, and the mitotic division of the embryo starts. This review highlights recent work that has shed light on the cytoskeletal structures that drive the meiotic divisions of the oocyte in mammals. In particular, we focus on how mammalian oocytes assemble a microtubule spindle in the absence of centrosomes, how they position the spindle in preparation for polar body extrusion, and how the spindle segregates the chromosomes. We primarily focus on mouse oocytes as a model system but also highlight recent insights from human oocytes.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"381-403"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100616-060553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36329813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-08-15DOI: 10.1146/annurev-cellbio-100617-062559
Christina Schoenherr, Margaret C Frame, Adam Byron
Cell adhesion to macromolecules in the microenvironment is essential for the development and maintenance of tissues, and its dysregulation can lead to a range of disease states, including inflammation, fibrosis, and cancer. The biomechanical and biochemical mechanisms that mediate cell adhesion rely on signaling by a range of effector proteins, including kinases and associated scaffolding proteins. The intracellular trafficking of these must be tightly controlled in space and time to enable effective cell adhesion and microenvironmental sensing and to integrate cell adhesion with, and compartmentalize it from, other cellular processes, such as gene transcription, protein degradation, and cell division. Delivery of adhesion receptors and signaling proteins from the plasma membrane to unanticipated subcellular locales is revealing novel biological functions. Here, we review the expected and unexpected trafficking, and sites of activity, of adhesion and growth factor receptors and intracellular kinase partners as we begin to appreciate the complexity and diversity of their spatial regulation.
{"title":"Trafficking of Adhesion and Growth Factor Receptors and Their Effector Kinases.","authors":"Christina Schoenherr, Margaret C Frame, Adam Byron","doi":"10.1146/annurev-cellbio-100617-062559","DOIUrl":"10.1146/annurev-cellbio-100617-062559","url":null,"abstract":"<p><p>Cell adhesion to macromolecules in the microenvironment is essential for the development and maintenance of tissues, and its dysregulation can lead to a range of disease states, including inflammation, fibrosis, and cancer. The biomechanical and biochemical mechanisms that mediate cell adhesion rely on signaling by a range of effector proteins, including kinases and associated scaffolding proteins. The intracellular trafficking of these must be tightly controlled in space and time to enable effective cell adhesion and microenvironmental sensing and to integrate cell adhesion with, and compartmentalize it from, other cellular processes, such as gene transcription, protein degradation, and cell division. Delivery of adhesion receptors and signaling proteins from the plasma membrane to unanticipated subcellular locales is revealing novel biological functions. Here, we review the expected and unexpected trafficking, and sites of activity, of adhesion and growth factor receptors and intracellular kinase partners as we begin to appreciate the complexity and diversity of their spatial regulation.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"29-58"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36400445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-07-20DOI: 10.1146/annurev-cellbio-100617-062855
Mara H Sherman
Stellate cells are resident lipid-storing cells of the pancreas and liver that transdifferentiate to a myofibroblastic state in the context of tissue injury. Beyond having roles in tissue homeostasis, stellate cells are increasingly implicated in pathological fibrogenic and inflammatory programs that contribute to tissue fibrosis and that constitute a growth-permissive tumor microenvironment. Although the capacity of stellate cells for extracellular matrix production and remodeling has long been appreciated, recent research efforts have demonstrated diverse roles for stellate cells in regulation of epithelial cell fate, immune modulation, and tissue health. Our present understanding of stellate cell biology in health and disease is discussed here, as are emerging means to target these multifaceted cells for therapeutic benefit.
{"title":"Stellate Cells in Tissue Repair, Inflammation, and Cancer.","authors":"Mara H Sherman","doi":"10.1146/annurev-cellbio-100617-062855","DOIUrl":"https://doi.org/10.1146/annurev-cellbio-100617-062855","url":null,"abstract":"<p><p>Stellate cells are resident lipid-storing cells of the pancreas and liver that transdifferentiate to a myofibroblastic state in the context of tissue injury. Beyond having roles in tissue homeostasis, stellate cells are increasingly implicated in pathological fibrogenic and inflammatory programs that contribute to tissue fibrosis and that constitute a growth-permissive tumor microenvironment. Although the capacity of stellate cells for extracellular matrix production and remodeling has long been appreciated, recent research efforts have demonstrated diverse roles for stellate cells in regulation of epithelial cell fate, immune modulation, and tissue health. Our present understanding of stellate cell biology in health and disease is discussed here, as are emerging means to target these multifaceted cells for therapeutic benefit.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"333-355"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100617-062855","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36329812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06DOI: 10.1146/annurev-cellbio-100617-062737
Robert G Parton
The plasma membrane of eukaryotic cells is not a simple sheet of lipids and proteins but is differentiated into subdomains with crucial functions. Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. The cellular functions of caveolae have long remained obscure, but a new molecular understanding of caveola formation has led to insights into their workings. Caveolae are formed by the coordinated action of a number of lipid-interacting proteins to produce a microdomain with a specific structure and lipid composition. Caveolae can bud from the plasma membrane to form an endocytic vesicle or can flatten into the membrane to help cells withstand mechanical stress. The role of caveolae as mechanoprotective and signal transduction elements is reviewed in the context of disease conditions associated with caveola dysfunction.
{"title":"Caveolae: Structure, Function, and Relationship to Disease.","authors":"Robert G Parton","doi":"10.1146/annurev-cellbio-100617-062737","DOIUrl":"https://doi.org/10.1146/annurev-cellbio-100617-062737","url":null,"abstract":"<p><p>The plasma membrane of eukaryotic cells is not a simple sheet of lipids and proteins but is differentiated into subdomains with crucial functions. Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. The cellular functions of caveolae have long remained obscure, but a new molecular understanding of caveola formation has led to insights into their workings. Caveolae are formed by the coordinated action of a number of lipid-interacting proteins to produce a microdomain with a specific structure and lipid composition. Caveolae can bud from the plasma membrane to form an endocytic vesicle or can flatten into the membrane to help cells withstand mechanical stress. The role of caveolae as mechanoprotective and signal transduction elements is reviewed in the context of disease conditions associated with caveola dysfunction.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"111-136"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100617-062737","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36566629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-05-11DOI: 10.1146/annurev-cellbio-100617-062818
C E Wagner, K M Wheeler, K Ribbeck
We review what is currently understood about how the structure of the primary solid component of mucus, the glycoprotein mucin, gives rise to the mechanical and biochemical properties of mucus that are required for it to perform its diverse physiological roles. Macroscale processes such as lubrication require mucus of a certain stiffness and spinnability, which are set by structural features of the mucin network, including the identity and density of cross-links and the degree of glycosylation. At the microscale, these same features affect the mechanical environment experienced by small particles and play a crucial role in establishing an interaction-based filter. Finally, mucin glycans are critical for regulating microbial interactions, serving as receptor binding sites for adhesion, as nutrient sources, and as environmental signals. We conclude by discussing how these structural principles can be used in the design of synthetic mucin-mimetic materials and provide suggestions for directions of future work in this field.
{"title":"Mucins and Their Role in Shaping the Functions of Mucus Barriers.","authors":"C E Wagner, K M Wheeler, K Ribbeck","doi":"10.1146/annurev-cellbio-100617-062818","DOIUrl":"10.1146/annurev-cellbio-100617-062818","url":null,"abstract":"<p><p>We review what is currently understood about how the structure of the primary solid component of mucus, the glycoprotein mucin, gives rise to the mechanical and biochemical properties of mucus that are required for it to perform its diverse physiological roles. Macroscale processes such as lubrication require mucus of a certain stiffness and spinnability, which are set by structural features of the mucin network, including the identity and density of cross-links and the degree of glycosylation. At the microscale, these same features affect the mechanical environment experienced by small particles and play a crucial role in establishing an interaction-based filter. Finally, mucin glycans are critical for regulating microbial interactions, serving as receptor binding sites for adhesion, as nutrient sources, and as environmental signals. We conclude by discussing how these structural principles can be used in the design of synthetic mucin-mimetic materials and provide suggestions for directions of future work in this field.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"189-215"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36566628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-07-20DOI: 10.1146/annurev-cellbio-100617-062826
Elisabetta Furlanis, Peter Scheiffele
Posttranscriptional mechanisms provide powerful means to expand the coding power of genomes. In nervous systems, alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of transcripts. Thus, alternative splicing programs play instructive roles in the development of neuronal cell type-specific properties, neuronal growth, self-recognition, synapse specification, and neuronal network function. Here we discuss the most recent genome-wide efforts on mapping RNA codes and RNA-binding proteins for neuronal alternative splicing regulation. We illustrate how alternative splicing shapes key steps of neuronal development, neuronal maturation, and synaptic properties. Finally, we highlight efforts to dissect the spatiotemporal dynamics of alternative splicing and their potential contribution to neuronal plasticity and the mature nervous system.
{"title":"Regulation of Neuronal Differentiation, Function, and Plasticity by Alternative Splicing.","authors":"Elisabetta Furlanis, Peter Scheiffele","doi":"10.1146/annurev-cellbio-100617-062826","DOIUrl":"https://doi.org/10.1146/annurev-cellbio-100617-062826","url":null,"abstract":"<p><p>Posttranscriptional mechanisms provide powerful means to expand the coding power of genomes. In nervous systems, alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of transcripts. Thus, alternative splicing programs play instructive roles in the development of neuronal cell type-specific properties, neuronal growth, self-recognition, synapse specification, and neuronal network function. Here we discuss the most recent genome-wide efforts on mapping RNA codes and RNA-binding proteins for neuronal alternative splicing regulation. We illustrate how alternative splicing shapes key steps of neuronal development, neuronal maturation, and synaptic properties. Finally, we highlight efforts to dissect the spatiotemporal dynamics of alternative splicing and their potential contribution to neuronal plasticity and the mature nervous system.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"451-469"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100617-062826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36329815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-07-25DOI: 10.1146/annurev-cellbio-100617-062508
Michele Curcio, Frank Bradke
After an injury in the adult mammalian central nervous system (CNS), lesioned axons fail to regenerate. This failure to regenerate contrasts with axons' remarkable potential to grow during embryonic development and after an injury in the peripheral nervous system (PNS). Several intracellular mechanisms-including cytoskeletal dynamics, axonal transport and trafficking, signaling and transcription of regenerative programs, and epigenetic modifications-control axon regeneration. In this review, we describe how manipulation of intrinsic mechanisms elicits a regenerative response in different organisms and how strategies are implemented to form the basis of a future regenerative treatment after CNS injury.
{"title":"Axon Regeneration in the Central Nervous System: Facing the Challenges from the Inside.","authors":"Michele Curcio, Frank Bradke","doi":"10.1146/annurev-cellbio-100617-062508","DOIUrl":"https://doi.org/10.1146/annurev-cellbio-100617-062508","url":null,"abstract":"<p><p>After an injury in the adult mammalian central nervous system (CNS), lesioned axons fail to regenerate. This failure to regenerate contrasts with axons' remarkable potential to grow during embryonic development and after an injury in the peripheral nervous system (PNS). Several intracellular mechanisms-including cytoskeletal dynamics, axonal transport and trafficking, signaling and transcription of regenerative programs, and epigenetic modifications-control axon regeneration. In this review, we describe how manipulation of intrinsic mechanisms elicits a regenerative response in different organisms and how strategies are implemented to form the basis of a future regenerative treatment after CNS injury.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"495-521"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100617-062508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36343835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-08-15DOI: 10.1146/annurev-cellbio-100617-062802
Eugene Oh, David Akopian, Michael Rape
Ubiquitylation is an essential posttranslational modification that controls cell division, differentiation, and survival in all eukaryotes. By combining multiple E3 ligases (writers), ubiquitin-binding effectors (readers), and de-ubiquitylases (erasers) with functionally distinct ubiquitylation tags, the ubiquitin system constitutes a powerful signaling network that is employed in similar ways from yeast to humans. Here, we discuss conserved principles of ubiquitin-dependent signaling that illustrate how this posttranslational modification shapes intracellular signaling networks to establish robust development and homeostasis throughout the eukaryotic kingdom.
{"title":"Principles of Ubiquitin-Dependent Signaling.","authors":"Eugene Oh, David Akopian, Michael Rape","doi":"10.1146/annurev-cellbio-100617-062802","DOIUrl":"https://doi.org/10.1146/annurev-cellbio-100617-062802","url":null,"abstract":"<p><p>Ubiquitylation is an essential posttranslational modification that controls cell division, differentiation, and survival in all eukaryotes. By combining multiple E3 ligases (writers), ubiquitin-binding effectors (readers), and de-ubiquitylases (erasers) with functionally distinct ubiquitylation tags, the ubiquitin system constitutes a powerful signaling network that is employed in similar ways from yeast to humans. Here, we discuss conserved principles of ubiquitin-dependent signaling that illustrate how this posttranslational modification shapes intracellular signaling networks to establish robust development and homeostasis throughout the eukaryotic kingdom.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"137-162"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100617-062802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36400443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-10-06Epub Date: 2018-08-15DOI: 10.1146/annurev-cellbio-100617-062527
Novalia Pishesha, Jessica R Ingram, Hidde L Ploegh
Molecular biologists and chemists alike have long sought to modify proteins with substituents that cannot be installed by standard or even advanced genetic approaches. We here describe the use of transpeptidases to achieve these goals. Living systems encode a variety of transpeptidases and peptide ligases that allow for the enzyme-catalyzed formation of peptide bonds, and protein engineers have used directed evolution to enhance these enzymes for biological applications. We focus primarily on the transpeptidase sortase A, which has become popular over the past few years for its ability to perform a remarkably wide variety of protein modifications, both in vitro and in living cells.
{"title":"Sortase A: A Model for Transpeptidation and Its Biological Applications.","authors":"Novalia Pishesha, Jessica R Ingram, Hidde L Ploegh","doi":"10.1146/annurev-cellbio-100617-062527","DOIUrl":"https://doi.org/10.1146/annurev-cellbio-100617-062527","url":null,"abstract":"<p><p>Molecular biologists and chemists alike have long sought to modify proteins with substituents that cannot be installed by standard or even advanced genetic approaches. We here describe the use of transpeptidases to achieve these goals. Living systems encode a variety of transpeptidases and peptide ligases that allow for the enzyme-catalyzed formation of peptide bonds, and protein engineers have used directed evolution to enhance these enzymes for biological applications. We focus primarily on the transpeptidase sortase A, which has become popular over the past few years for its ability to perform a remarkably wide variety of protein modifications, both in vitro and in living cells.</p>","PeriodicalId":7944,"journal":{"name":"Annual review of cell and developmental biology","volume":"34 ","pages":"163-188"},"PeriodicalIF":11.3,"publicationDate":"2018-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cellbio-100617-062527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36400444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}