Endocytosis is a fundamental mechanism by which cells perform housekeeping functions. It occurs via a variety of mechanisms and involves many regulatory proteins. The GTPase dynamin acts as a "molecular scissor" to form endocytic vesicles and is a critical regulator among the proteins involved in endocytosis. Some GTPases (e.g., Cdc42, arf6, RhoA), membrane proteins (e.g., flotillins, tetraspanins), and secondary messengers (e.g., calcium) mediate dynamin-independent endocytosis. These pathways may be convergent, as multiple pathways exist in a single cell. However, what determines the specific path of endocytosis is complex and challenging to comprehend. This review summarizes the mechanisms of dynamin-independent endocytosis, the involvement of microRNAs, and factors that contribute to the cellular decision about the specific route of endocytosis.
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http://dx.doi.org/10.3390/cells11162557 | DOI Listing |
PLoS Pathog
November 2024
Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Mammalian receptor-mediated endocytosis (RME) often involves at least one of three isoforms of the large GTPase dynamin (Dyn). Dyn pinches-off vesicles at the plasma membrane and mediates uptake of many viruses, although some viruses directly penetrate the plasma membrane. RME is classically interrogated by genetic and pharmacological interference, but this has been hampered by undesired effects.
View Article and Find Full Text PDFJ Physiol
November 2024
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
J Physiol
August 2024
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
Dynamins are GTPases required for pinching vesicles off the plasma membrane once a critical curvature is reached during endocytosis. Here, we probed dynamin function in central synapses by depleting all three dynamin isoforms in postnatal hippocampal neurons down to negligible levels. We found a decrease in the propensity of evoked neurotransmission as well as a reduction in synaptic vesicle numbers.
View Article and Find Full Text PDFMol Pharm
July 2024
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.
Understanding the internalization of nanosized particles by mucosal epithelial cells is essential in a number of areas including viral entry at mucosal surfaces, nanoplastic pollution, as well as design and development of nanotechnology-type medicines. Here, we report our comparative study on pathways of cellular internalization in epithelial Caco-2 cells cultured in vitro as either a polarized, differentiated cell layer or as nonpolarized, nondifferentiated cells. The study reveals a number of differences in the extent that endocytic processes are used by cells, depending on their differentiation status and the nature of applied nanoparticles.
View Article and Find Full Text PDFbioRxiv
February 2024
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Clathrin/dynamin-independent endocytosis of ordered plasma membrane domains (rdered embrane omain ndocytosis, OMDE) can become massive in response to cytoplasmic Ca elevations, G protein activation by non-hydrolyzable GTP analogs, and enhanced oxidative metabolism. In patch-clamped murine bone marrow macrophages (BMMs), cytoplasmic succinate and pyruvate, but not β-hydroxybutyrate, induce OMDE of 75% of the plasma membrane within 2 min. The responses require palmitoylation of membrane proteins, being decreased by 70% in BMMs lacking the acyltransferase, DHHC5, by treatment with carnitine to shift long-chain acyl groups from cytoplasmic to mitochondrial acyl-CoAs, by bromopalmitate/albumin complexes to block DHHCs, and by the mitochondria-specific cyclosporin, NIM811, to block permeability transition pores that may release mitochondrial coenzyme A into the cytoplasm.
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