Multiple modes of endophilin-mediated conversion of lipid vesicles into coated tubes: implications for synaptic endocytosis.

J Biol Chem

Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Published: July 2010

Endophilin A1 is a BAR (Bin/amphiphysin/Rvs) protein abundant in neural synapses that senses and induces membrane curvature, contributing to neck formation in presynaptic endocytic vesicles. To investigate its role in membrane remodeling, we used cryoelectron microscopy to characterize structural changes induced in lipid vesicles by exposure to endophilin. The vesicles convert rapidly to coated tubules whose morphology reflects the local concentration of endophilin. Their diameters and curvature resemble those of synaptic vesicles in situ. Three-dimensional reconstructions of quasicylindrical tubes revealed arrays of BAR dimers, flanked by densities that we equate with amphipathic helices whose folding and membrane insertion were attested by EPR. We also observed the compression of bulbous coated tubes into 70-A-wide cylindrical micelles, which appear to mimic the penultimate (hemi-fission) stage of endocytosis. Our findings suggest that the adaptability of endophilin-lipid interactions underlies dynamic changes of endocytic membranes.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906327PMC
http://dx.doi.org/10.1074/jbc.M110.143776DOI Listing

Publication Analysis

Top Keywords

lipid vesicles
8
coated tubes
8
vesicles
5
multiple modes
4
modes endophilin-mediated
4
endophilin-mediated conversion
4
conversion lipid
4
vesicles coated
4
tubes implications
4
implications synaptic
4

Similar Publications

Translocation across barriers and through constrictions is a mechanism that is often used in vivo for transporting material between compartments. A specific example is apicomplexan parasites invading host cells through the tight junction that acts as a pore, and a similar barrier crossing is involved in drug delivery using lipid vesicles penetrating intact skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii.

View Article and Find Full Text PDF

Mapping organism-wide single cell mRNA expression linked to extracellular vesicle biogenesis, secretion and cargo.

Function (Oxf)

January 2025

Department of Health and Exercise Science, College of Health and Human Sciences, Colorado State University, Fort Collins, CO, USA.

Extracellular vesicles (EVs) are functional lipid-bound nanoparticles trafficked between cells and found in every biofluid. It is widely claimed that EVs can be secreted by every cell, but the quantity and composition of these EVs can differ greatly among cell types and tissues. Defining this heterogeneity has broad implications for EV-based communication in health and disease.

View Article and Find Full Text PDF

Clinical studies of blood-borne Extracellular vesicles in psychiatry: A systematic review.

J Psychiatr Res

January 2025

Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379, Oslo, Norway; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway; Department for Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway.

Biomarkers for the diagnosis and clinical management of psychiatric disorders are currently lacking. Extracellular vesicles (EVs), lipid membrane-encapsulated vesicles released by cells, hold promise as a source of biomarkers due to their ability to carry molecules that reflect the status of their donor cells and their ubiquitous presence in biofluids. This review examines the literature on EVs in biofluids from psychiatric disorder patients, and discuss how the published studies contribute to our understanding of the pathophysiology of these conditions and to the discovery of potential biomarkers.

View Article and Find Full Text PDF

Background: Sclerostin (SOST) is traditionally regarded as an osteocyte-derived secreted glycoprotein that regulates bone mineralization. Recent studies reported that SOST is also released from non-skeletal sources, especially during inflammation. However, the cellular source and regulatory mechanisms governing SOST generation in inflammation remain unclear.

View Article and Find Full Text PDF

Cellular Cholesterol Loss Impairs Synaptic Vesicle Mobility via the CAMK2/Synapsin-1 Signaling Pathway.

Front Biosci (Landmark Ed)

January 2025

Department of Neurology, Jinshan Hospital, Fudan University, 201508 Shanghai, China.

Background: Neuronal cholesterol deficiency may contribute to the synaptopathy observed in Alzheimer's disease (AD). However, the underlying mechanisms remain poorly understood. Intact synaptic vesicle (SV) mobility is crucial for normal synaptic function, whereas disrupted SV mobility can trigger the synaptopathy associated with AD.

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!