Cargando…

Molecular mechanism of Fast Endophilin-Mediated Endocytosis

Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Clathrin-mediated endocytosis (CME) is the housekeeping pathway in resting cells but additional Clathrin-independent endocytic (CIE) routes, including Fast Endophilin-Mediated Endocytosis (FEME), internalize specif...

Descripción completa

Detalles Bibliográficos
Autores principales: Casamento, Alessandra, Boucrot, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319585/
https://www.ncbi.nlm.nih.gov/pubmed/32589750
http://dx.doi.org/10.1042/BCJ20190342
_version_ 1783551083960860672
author Casamento, Alessandra
Boucrot, Emmanuel
author_facet Casamento, Alessandra
Boucrot, Emmanuel
author_sort Casamento, Alessandra
collection PubMed
description Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Clathrin-mediated endocytosis (CME) is the housekeeping pathway in resting cells but additional Clathrin-independent endocytic (CIE) routes, including Fast Endophilin-Mediated Endocytosis (FEME), internalize specific cargoes and support diverse cellular functions. FEME is part of the Dynamin-dependent subgroup of CIE pathways. Here, we review our current understanding of the molecular mechanism of FEME. Key steps are: (i) priming, (ii) cargo selection, (iii) membrane curvature and carrier formation, (iv) membrane scission and (v) cytosolic transport. All steps are controlled by regulatory mechanisms mediated by phosphoinositides and by kinases such as Src, LRRK2, Cdk5 and GSK3β. A key feature of FEME is that it is not constitutively active but triggered upon the stimulation of selected cell surface receptors by their ligands. In resting cells, there is a priming cycle that concentrates Endophilin into clusters on discrete locations of the plasma membrane. In the absence of receptor activation, the patches quickly abort and new cycles are initiated nearby, constantly priming the plasma membrane for FEME. Upon activation, receptors are swiftly sorted into pre-existing Endophilin clusters, which then bud to form FEME carriers within 10 s. We summarize the hallmarks of FEME and the techniques and assays required to identify it. Next, we review similarities and differences with other CIE pathways and proposed cargoes that may use FEME to enter cells. Finally, we submit pending questions and future milestones and discuss the exciting perspectives that targeting FEME may boost treatments against cancer and neurodegenerative diseases.
format Online
Article
Text
id pubmed-7319585
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-73195852020-06-30 Molecular mechanism of Fast Endophilin-Mediated Endocytosis Casamento, Alessandra Boucrot, Emmanuel Biochem J Cell Membranes, Excitation & Transport Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Clathrin-mediated endocytosis (CME) is the housekeeping pathway in resting cells but additional Clathrin-independent endocytic (CIE) routes, including Fast Endophilin-Mediated Endocytosis (FEME), internalize specific cargoes and support diverse cellular functions. FEME is part of the Dynamin-dependent subgroup of CIE pathways. Here, we review our current understanding of the molecular mechanism of FEME. Key steps are: (i) priming, (ii) cargo selection, (iii) membrane curvature and carrier formation, (iv) membrane scission and (v) cytosolic transport. All steps are controlled by regulatory mechanisms mediated by phosphoinositides and by kinases such as Src, LRRK2, Cdk5 and GSK3β. A key feature of FEME is that it is not constitutively active but triggered upon the stimulation of selected cell surface receptors by their ligands. In resting cells, there is a priming cycle that concentrates Endophilin into clusters on discrete locations of the plasma membrane. In the absence of receptor activation, the patches quickly abort and new cycles are initiated nearby, constantly priming the plasma membrane for FEME. Upon activation, receptors are swiftly sorted into pre-existing Endophilin clusters, which then bud to form FEME carriers within 10 s. We summarize the hallmarks of FEME and the techniques and assays required to identify it. Next, we review similarities and differences with other CIE pathways and proposed cargoes that may use FEME to enter cells. Finally, we submit pending questions and future milestones and discuss the exciting perspectives that targeting FEME may boost treatments against cancer and neurodegenerative diseases. Portland Press Ltd. 2020-06-26 2020-06-26 /pmc/articles/PMC7319585/ /pubmed/32589750 http://dx.doi.org/10.1042/BCJ20190342 Text en © 2020 The Author(s) https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . Open access for this article was enabled by the participation of University College London in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC.
spellingShingle Cell Membranes, Excitation & Transport
Casamento, Alessandra
Boucrot, Emmanuel
Molecular mechanism of Fast Endophilin-Mediated Endocytosis
title Molecular mechanism of Fast Endophilin-Mediated Endocytosis
title_full Molecular mechanism of Fast Endophilin-Mediated Endocytosis
title_fullStr Molecular mechanism of Fast Endophilin-Mediated Endocytosis
title_full_unstemmed Molecular mechanism of Fast Endophilin-Mediated Endocytosis
title_short Molecular mechanism of Fast Endophilin-Mediated Endocytosis
title_sort molecular mechanism of fast endophilin-mediated endocytosis
topic Cell Membranes, Excitation & Transport
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319585/
https://www.ncbi.nlm.nih.gov/pubmed/32589750
http://dx.doi.org/10.1042/BCJ20190342
work_keys_str_mv AT casamentoalessandra molecularmechanismoffastendophilinmediatedendocytosis
AT boucrotemmanuel molecularmechanismoffastendophilinmediatedendocytosis