Amir Shee, Vidur Sabharwal, Sandhya P. Koushika, Amitabha Nandi, Debasish Chaudhuri
{"title":"UNC-104 transport properties are robust and independent of changes in its cargo binding","authors":"Amir Shee, Vidur Sabharwal, Sandhya P. Koushika, Amitabha Nandi, Debasish Chaudhuri","doi":"arxiv-2409.02655","DOIUrl":null,"url":null,"abstract":"Cargo distribution within eukaryotic cells relies on the active transport\nmechanisms driven by molecular motors. Despite their critical role, the\nintricate relationship between motor transport properties and cargo binding -\nand its impact on motor distribution - remains inadequately understood.\nAdditionally, improper regulation of ubiquitination, a pivotal\npost-translational modification that affects protein degradation, activation,\nand localization, is associated with several neurodegenerative diseases. Recent\ndata showed that ubiquitination can alter motor-cargo binding of the Kinesin-3\nmotor UNC-104 / KIF1A that transports synaptic vesicles. To investigate how\nubiquitin-like modifications affect motor protein function, particularly cargo\nbinding, transport properties, and distribution, we utilize the PLM neuron of\nC. elegans as a model system. Using fluorescent microscopy, we assess the\ndistribution of cargo-bound UNC-104 motors along the axon and probe their\ndynamics using FRAP experiments. We model cargo binding kinetics with a Master\nequation and motor density dynamics using a Fokker-Planck approach. Our\ncombined experimental and theoretical analysis reveals that ubiquitin-like\nknockdowns enhance UNC-104's cooperative binding to its cargo. However, these\nmodifications do not affect UNC-104's transport properties, such as\nprocessivity and diffusivity. Thus, while ubiquitin-like modifications\nsignificantly impact the cargo-binding of UNC-104, they do not alter its\ntransport dynamics, keeping the homeostatic distribution of UNC-104 unchanged.","PeriodicalId":501040,"journal":{"name":"arXiv - PHYS - Biological Physics","volume":"59 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"arXiv - PHYS - Biological Physics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/arxiv-2409.02655","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Cargo distribution within eukaryotic cells relies on the active transport
mechanisms driven by molecular motors. Despite their critical role, the
intricate relationship between motor transport properties and cargo binding -
and its impact on motor distribution - remains inadequately understood.
Additionally, improper regulation of ubiquitination, a pivotal
post-translational modification that affects protein degradation, activation,
and localization, is associated with several neurodegenerative diseases. Recent
data showed that ubiquitination can alter motor-cargo binding of the Kinesin-3
motor UNC-104 / KIF1A that transports synaptic vesicles. To investigate how
ubiquitin-like modifications affect motor protein function, particularly cargo
binding, transport properties, and distribution, we utilize the PLM neuron of
C. elegans as a model system. Using fluorescent microscopy, we assess the
distribution of cargo-bound UNC-104 motors along the axon and probe their
dynamics using FRAP experiments. We model cargo binding kinetics with a Master
equation and motor density dynamics using a Fokker-Planck approach. Our
combined experimental and theoretical analysis reveals that ubiquitin-like
knockdowns enhance UNC-104's cooperative binding to its cargo. However, these
modifications do not affect UNC-104's transport properties, such as
processivity and diffusivity. Thus, while ubiquitin-like modifications
significantly impact the cargo-binding of UNC-104, they do not alter its
transport dynamics, keeping the homeostatic distribution of UNC-104 unchanged.