Endocytosis in non-neuronal cells requires gradual recruitment of proteins to endocytic sites for inducing membrane curvature and forming contractile scaffolds around the neck of endocytic pits. This recruitment process is thought to be rate-limiting, requiring tens of seconds. In contrast, a form of endocytosis in neurons called ultrafast endocytosis is much faster, requiring only 100 milliseconds for endocytosis of synaptic vesicle proteins. In this review, we compare the mechanisms of protein recruitment during clathrin-mediated endocytosis in non-neuronal cells and ultrafast endocytosis in neurons and discuss how endocytosis can complete within 100 milliseconds. We then discuss the potential clinical relevance of this endocytic pathway.
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http://dx.doi.org/10.1152/physiol.00041.2024 | DOI Listing |
Physiology (Bethesda)
March 2025
Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe St. Baltimore MD, 21205 USA.
Endocytosis in non-neuronal cells requires gradual recruitment of proteins to endocytic sites for inducing membrane curvature and forming contractile scaffolds around the neck of endocytic pits. This recruitment process is thought to be rate-limiting, requiring tens of seconds. In contrast, a form of endocytosis in neurons called ultrafast endocytosis is much faster, requiring only 100 milliseconds for endocytosis of synaptic vesicle proteins.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Cell Biology, The Johns Hopkins University, Baltimore MD, 21205, USA.
Live human brain tissues provide unique opportunities for understanding the physiology and pathophysiology of synaptic transmission. Investigations have been limited to anatomy, electrophysiology, and protein localization-while crucial parameters such as synaptic vesicle dynamics were not visualized. Here we utilize zap-and-freeze time-resolved electron microscopy to overcome this hurdle.
View Article and Find Full Text PDFJ Neurosci
September 2024
Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China
Ribbon synapses of inner hair cells (IHCs) are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles (SVs), however, remains elusive. This study showed that hair cell knock-out of murine , whose human homolog is responsible for nonsyndromic sensorineural hearing loss DFNA71, resulted in auditory synaptopathy by impairing synaptic endocytosis and recycling.
View Article and Find Full Text PDFEMBO J
August 2024
Instituto de Biomedicina de Sevilla (IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla), Dpto. de Fisiología Médica y Biofísica, Facultad de Medicina, and CIBERNED ISCIII, Seville, Spain.
Brain function relies on quick inter-neuron communication at specialized points of contact termed synapses. In the latest issue of The EMBO Journal, Imoto, Xue, et al (2024) report the discovery of a novel, regulated interaction between two major endocytosis players which supports the notion of a preassembled protein machinery at presynaptic nerve terminals that can explain how the high speed of ultrafast endocytosis is possible.
View Article and Find Full Text PDFEMBO J
August 2024
Cell Signalling Unit, Children's Medical Research Institute, The University of Sydney, Locked Bag 23, Wentworthville, 2145, NSW, Australia.
Dynamin 1 mediates fission of endocytic synaptic vesicles in the brain and has two major splice variants, Dyn1xA and Dyn1xB, which are nearly identical apart from the extended C-terminal region of Dyn1xA. Despite a similar set of binding partners, only Dyn1xA is enriched at endocytic zones and accelerates vesicle fission during ultrafast endocytosis. Here, we report that Dyn1xA achieves this localization by preferentially binding to Endophilin A1 through a newly defined binding site within its long C-terminal tail extension.
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