Biology of the Cell最新文献

The Notch signalling receptor is a mechanoreceptor that is activated by force. This force elicits a conformational change in Notch that results in the release of its intracellular domain into the cytosol by two consecutive proteolytic cleavages. In most cases, the force is generated by pulling of the ligands on the receptor upon their endocytosis. In this review, we summarise recent work that shed a more detailed light on the role of endocytosis during ligand-dependent Notch activation and discuss the role of ubiquitylation of the ligands during this process.

Mitochondria are organelles involved in various functions related to cellular metabolism and homoeostasis. Though mitochondria contain own genome, their nuclear counterparts encode most of the different mitochondrial proteins. These are synthesised as precursors in the cytosol and have to be delivered into the mitochondria. These organelles hence have elaborate machineries for the import of precursor proteins from cytosol. The protein import machineries present in both mitochondrial membrane and aqueous compartments show great variability in pre-protein recognition, translocation and sorting across or into it. Mitochondrial protein import machineries also interact transiently with other protein complexes of the respiratory chain or those involved in the maintenance of membrane architecture. Hence mitochondrial protein translocation is an indispensable part of the regulatory network that maintains protein biogenesis, bioenergetics, membrane dynamics and quality control of the organelle. Various stress conditions and diseases that are associated with mitochondrial import defects lead to changes in cellular transcriptomic and proteomic profiles. Dysfunction in mitochondrial protein import also causes over-accumulation of precursor proteins and their aggregation in the cytosol. Multiple pathways may be activated for buffering these harmful consequences. Here, we present a comprehensive picture of import machinery and its role in cellular quality control in response to defective mitochondrial import. We also discuss the pathological consequences of dysfunctional mitochondrial protein import in neurodegeneration and cancer.

Inside living cells, the remodelling of membrane tubules by actomyosin networks is crucial for processes such as intracellular trafficking or organelle reshaping. In this review, we first present various in vivo situations in which actin affects membrane tubule remodelling, then we recall some results on force production by actin dynamics and on membrane tubules physics. Finally, we show that our knowledge of the underlying mechanisms by which actomyosin dynamics affect tubule morphology has recently been moved forward. This is thanks to in vitro experiments that mimic cellular membranes and actin dynamics and allow deciphering the physics of tubule remodelling in biochemically controlled conditions, and shed new light on tubule shape regulation.

Deformability of the plasma membrane, the outermost surface of metazoan cells, allows cells to be dynamic, mobile and flexible. Factors that affect this deformability, such as tension on the membrane, can regulate a myriad of cellular functions, including membrane resealing, cell motility, polarisation, shape maintenance, membrane area control and endocytic vesicle trafficking. This review focuses on mechanoregulation of clathrin-mediated endocytosis (CME). We first delineate the origins of cell membrane tension and the factors that yield to its spatial and temporal fluctuations within cells. We then review the recent literature demonstrating that tension on the membrane is a fast-acting and reversible regulator of CME. Finally, we discuss tension-based regulation of endocytic clathrin coat formation during physiological processes.

Nuclear lamins are type V intermediate filament proteins that form a filamentous meshwork beneath the inner nuclear membrane. Additionally, a sub-population of A- and B-type lamins localizes in the nuclear interior. The nuclear lamina protects the nucleus from mechanical stress and mediates nucleo-cytoskeletal coupling. Lamins form a scaffold that partially tethers chromatin at the nuclear envelope. The nuclear lamina also stabilises protein–protein interactions involved in gene regulation and DNA repair. The lamin-based protein sub-complexes are implicated in both nuclear and cytoskeletal organisation, the mechanical stability of the nucleus, genome organisation, transcriptional regulation, genome stability and cellular differentiation. Here, we review recent research on nuclear lamins and unique roles of A- and B-type lamins in modulating various nuclear processes and their impact on cell function.