Clathrin, adaptors and disease: insights from the yeast Saccharomyces cerevisiae.

Front Biosci (Landmark Ed)

Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Published: June 2013

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.

Download full-text PDF

Source
http://dx.doi.org/10.2741/4149DOI Listing

Publication Analysis

Top Keywords

clathrin adaptors
8
yeast saccharomyces
8
saccharomyces cerevisiae
8
clathrin-mediated trafficking
8
trafficking pathways
8
trafficking events
8
clathrin
5
adaptors disease
4
disease insights
4
yeast
4

Similar Publications

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 PDF

RPS23RG1 inhibits SORT1-mediated lysosomal degradation of MDGA2 to protect against autism.

Theranostics

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 PDF

Investigating Complexin-Membrane Interactions Using NMR and Optical Methods.

Methods 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 PDF

Molecular Dynamics Simulations of the SNARE Complex Interacting with Synaptotagmin, Complexin, and Lipid Bilayers.

Methods 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 PDF
Article Synopsis
  • Recent research indicates that blocking the RIPK1/RIPK3/MLKL necrosome can help reduce inflammatory pain linked to conditions like demyelination in the central nervous system.
  • This study tests necrostatin-1s (Nec-1s), a specific RIPK1 inhibitor, on LPS-induced inflammatory pain in male mice, assessing pain sensitivity through hot plate tests and examining related protein changes.
  • Results show that Nec-1s not only prevents LPS-induced pain relief but also reverses the activation of key proteins and signals involved in inflammation and demyelination, suggesting that RIPK1 inhibitors could be a promising treatment for managing inflammatory pain.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!