Since the identification of clathrin as a vesicular coat protein, numerous studies have contributed to our understanding of the role of clathrin and clathrin-mediated trafficking pathways in cell function. The budding yeast, Saccharomyces cerevisiae, offers a wealth of highly developed approaches that have been applied to study clathrin-mediated trafficking events, most of which are conserved in mammalian cells. Here we review the function of clathrin and clathrin adaptors in yeast. We also discuss the role of these proteins in human disease and how certain pathogens have co-opted trafficking pathways for their own use. These studies highlight the advantages of studying complex trafficking events using yeast as a model.
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http://dx.doi.org/10.2741/4149 | DOI Listing |
Cell Mol Life Sci
January 2025
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
C1orf115 has been identified in high-throughput screens as a regulator of multidrug resistance possibly mediated through an interaction with ATP-dependent membrane transporter ABCB1. Here we show that C1orf115 not only shares structural similarities with FACI/C11orf86 to interact with clathrin adaptors to undergo endocytosis, but also induces ABCA1 transcription to promote cholesterol efflux. C1orf115 consists of an N-terminal intrinsically disordered region and a C-terminal α-helix.
View Article and Find Full Text PDFTheranostics
January 2025
Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Mutations in the synaptic protein MAM domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) have been associated with autism spectrum disorder (ASD). Therefore, elucidating the regulatory mechanisms of MDGA2 can help develop effective treatments for ASD. Liquid chromatography-tandem mass spectrometry was carried out to identify proteins interacting with the extracellular domain of RPS23RG1 and with MDGA2, followed by co-immunoprecipitation assays to confirm protein-protein interactions.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
Complexins are a family of small presynaptic proteins that regulate neurotransmitter release at nerve terminals and are highly conserved in evolution. While direct interactions with SNARE proteins are critical for all complexin functions, binding of their disordered C-terminal domains (CTD) to membranes, especially to synaptic vesicle membranes, is essential for the ability of complexin to inhibit vesicle release. Furthermore, while some complexin CTDs possess an endogenous affinity for membranes, other complexin isoforms are subject to lipidation at their C-termini, which is presumed to confer additional membrane binding.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Departments of Neurology, and Anatomy and Cell Biology, Wayne State University School of Medicine, University Health Center, Detroit, MI, USA.
Molecular dynamics (MD) simulations enable in silico investigation of the dynamic behavior of proteins and protein complexes. Here, we describe MD simulations of the SNARE bundle forming the complex with the neuronal proteins Synaptotagmin-1 (Syt1) and Complexin (Cpx). Syt1 is the synaptic vesicle (SV) protein that serves as the neuronal calcium sensor and triggers synaptic fusion upon calcium binding, and this process is promoted and accelerated by Cpx.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
January 2025
Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, Türkiye.
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