Cargando…

LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation

During autophagy, actin filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to actin assembly are poorly understoo...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Xiaohua, Mullins, R. Dyche
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314544/
https://www.ncbi.nlm.nih.gov/pubmed/30420355
http://dx.doi.org/10.1083/jcb.201802157
_version_ 1783384114160730112
author Hu, Xiaohua
Mullins, R. Dyche
author_facet Hu, Xiaohua
Mullins, R. Dyche
author_sort Hu, Xiaohua
collection PubMed
description During autophagy, actin filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to actin assembly are poorly understood. We show that, in nonstarved cells, cytoplasmic JMY colocalizes with STRAP, a regulator of JMY’s nuclear functions, on nonmotile vesicles with no associated actin networks. Upon starvation, JMY shifts to motile, LC3-containing membranes that move on actin comet tails. LC3 enhances JMY’s de novo actin nucleation activity via a cryptic actin-binding sequence near JMY’s N terminus, and STRAP inhibits JMY’s ability to nucleate actin and activate the Arp2/3 complex. Cytoplasmic STRAP negatively regulates autophagy. Finally, we use purified proteins to reconstitute LC3- and JMY-dependent actin network formation on membranes and inhibition of network formation by STRAP. We conclude that LC3 and STRAP regulate JMY’s actin assembly activities in trans during autophagy.
format Online
Article
Text
id pubmed-6314544
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-63145442019-01-09 LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation Hu, Xiaohua Mullins, R. Dyche J Cell Biol Research Articles During autophagy, actin filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to actin assembly are poorly understood. We show that, in nonstarved cells, cytoplasmic JMY colocalizes with STRAP, a regulator of JMY’s nuclear functions, on nonmotile vesicles with no associated actin networks. Upon starvation, JMY shifts to motile, LC3-containing membranes that move on actin comet tails. LC3 enhances JMY’s de novo actin nucleation activity via a cryptic actin-binding sequence near JMY’s N terminus, and STRAP inhibits JMY’s ability to nucleate actin and activate the Arp2/3 complex. Cytoplasmic STRAP negatively regulates autophagy. Finally, we use purified proteins to reconstitute LC3- and JMY-dependent actin network formation on membranes and inhibition of network formation by STRAP. We conclude that LC3 and STRAP regulate JMY’s actin assembly activities in trans during autophagy. Rockefeller University Press 2019-01-07 /pmc/articles/PMC6314544/ /pubmed/30420355 http://dx.doi.org/10.1083/jcb.201802157 Text en © 2018 Hu and Mullins https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Hu, Xiaohua
Mullins, R. Dyche
LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
title LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
title_full LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
title_fullStr LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
title_full_unstemmed LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
title_short LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
title_sort lc3 and strap regulate actin filament assembly by jmy during autophagosome formation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314544/
https://www.ncbi.nlm.nih.gov/pubmed/30420355
http://dx.doi.org/10.1083/jcb.201802157
work_keys_str_mv AT huxiaohua lc3andstrapregulateactinfilamentassemblybyjmyduringautophagosomeformation
AT mullinsrdyche lc3andstrapregulateactinfilamentassemblybyjmyduringautophagosomeformation