Activation Mechanisms of the VPS34 Complexes

Phosphatidylinositol-3-phosphate (PtdIns(3)P) is essential for cell survival, and its intracellular synthesis is spatially and temporally regulated. It has major roles in two distinctive cellular pathways, namely, the autophagy and endocytic pathways. PtdIns(3)P is synthesized from phosphatidylinosi...

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Autor principal:	Yohei Ohashi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	VPS34 PtdIns(3)P VPS15 Beclin 1 ATG14L UVRAG Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1447c4c5f1e14934a497d0dd195420f8
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spelling	oai:doaj.org-article:1447c4c5f1e14934a497d0dd195420f82021-11-25T17:11:46ZActivation Mechanisms of the VPS34 Complexes10.3390/cells101131242073-4409https://doaj.org/article/1447c4c5f1e14934a497d0dd195420f82021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3124https://doaj.org/toc/2073-4409Phosphatidylinositol-3-phosphate (PtdIns(3)P) is essential for cell survival, and its intracellular synthesis is spatially and temporally regulated. It has major roles in two distinctive cellular pathways, namely, the autophagy and endocytic pathways. PtdIns(3)P is synthesized from phosphatidylinositol (PtdIns) by PIK3C3C/VPS34 in mammals or Vps34 in yeast. Pathway-specific VPS34/Vps34 activity is the consequence of the enzyme being incorporated into two mutually exclusive complexes: complex I for autophagy, composed of VPS34/Vps34–Vps15/Vps15-Beclin 1/Vps30-ATG14L/Atg14 (mammals/yeast), and complex II for endocytic pathways, in which ATG14L/Atg14 is replaced with UVRAG/Vps38 (mammals/yeast). Because of its involvement in autophagy, defects in which are closely associated with human diseases such as cancer and neurodegenerative diseases, developing highly selective drugs that target specific VPS34/Vps34 complexes is an essential goal in the autophagy field. Recent studies on the activation mechanisms of VPS34/Vps34 complexes have revealed that a variety of factors, including conformational changes, lipid physicochemical parameters, upstream regulators, and downstream effectors, greatly influence the activity of these complexes. This review summarizes and highlights each of these influences as well as clarifying key questions remaining in the field and outlining future perspectives.Yohei OhashiMDPI AGarticleVPS34PtdIns(3)PVPS15Beclin 1ATG14LUVRAGBiology (General)QH301-705.5ENCells, Vol 10, Iss 3124, p 3124 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	VPS34 PtdIns(3)P VPS15 Beclin 1 ATG14L UVRAG Biology (General) QH301-705.5
spellingShingle	VPS34 PtdIns(3)P VPS15 Beclin 1 ATG14L UVRAG Biology (General) QH301-705.5 Yohei Ohashi Activation Mechanisms of the VPS34 Complexes
description	Phosphatidylinositol-3-phosphate (PtdIns(3)P) is essential for cell survival, and its intracellular synthesis is spatially and temporally regulated. It has major roles in two distinctive cellular pathways, namely, the autophagy and endocytic pathways. PtdIns(3)P is synthesized from phosphatidylinositol (PtdIns) by PIK3C3C/VPS34 in mammals or Vps34 in yeast. Pathway-specific VPS34/Vps34 activity is the consequence of the enzyme being incorporated into two mutually exclusive complexes: complex I for autophagy, composed of VPS34/Vps34–Vps15/Vps15-Beclin 1/Vps30-ATG14L/Atg14 (mammals/yeast), and complex II for endocytic pathways, in which ATG14L/Atg14 is replaced with UVRAG/Vps38 (mammals/yeast). Because of its involvement in autophagy, defects in which are closely associated with human diseases such as cancer and neurodegenerative diseases, developing highly selective drugs that target specific VPS34/Vps34 complexes is an essential goal in the autophagy field. Recent studies on the activation mechanisms of VPS34/Vps34 complexes have revealed that a variety of factors, including conformational changes, lipid physicochemical parameters, upstream regulators, and downstream effectors, greatly influence the activity of these complexes. This review summarizes and highlights each of these influences as well as clarifying key questions remaining in the field and outlining future perspectives.
format	article
author	Yohei Ohashi
author_facet	Yohei Ohashi
author_sort	Yohei Ohashi
title	Activation Mechanisms of the VPS34 Complexes
title_short	Activation Mechanisms of the VPS34 Complexes
title_full	Activation Mechanisms of the VPS34 Complexes
title_fullStr	Activation Mechanisms of the VPS34 Complexes
title_full_unstemmed	Activation Mechanisms of the VPS34 Complexes
title_sort	activation mechanisms of the vps34 complexes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1447c4c5f1e14934a497d0dd195420f8
work_keys_str_mv	AT yoheiohashi activationmechanismsofthevps34complexes
_version_	1718412633738051584

Activation Mechanisms of the VPS34 Complexes

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