The ARF GAP ELMOD2 acts with different GTPases to regulate centrosomal microtubule nucleation and cytokinesis.
ADP-Ribosylation Factors
/ metabolism
Animals
Cell Culture Techniques
Centrosome
/ metabolism
Cytokinesis
/ physiology
Cytoskeletal Proteins
/ genetics
Fibroblasts
/ metabolism
GTP-Binding Proteins
/ metabolism
GTPase-Activating Proteins
/ metabolism
Mice
Microtubule-Associated Proteins
/ metabolism
Microtubules
/ metabolism
Mitochondria
/ metabolism
Mouse Embryonic Stem Cells
/ metabolism
Journal
Molecular biology of the cell
ISSN: 1939-4586
Titre abrégé: Mol Biol Cell
Pays: United States
ID NLM: 9201390
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
pubmed:
3
7
2020
medline:
4
6
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
ELMOD2 is a ∼32 kDa protein first purified by its GTPase-activating protein (GAP) activity toward ARL2 and later shown to have uniquely broad specificity toward ARF family GTPases in in vitro assays. To begin the task of defining its functions in cells, we deleted ELMOD2 in immortalized mouse embryonic fibroblasts and discovered a number of cellular defects, which are reversed upon expression of ELMOD2-myc. We show that these defects, resulting from the loss of ELMOD2, are linked to two different pathways and two different GTPases: with ARL2 and TBCD to support microtubule nucleation from centrosomes and with ARF6 in cytokinesis. These data highlight key aspects of signaling by ARF family GAPs that contribute to previously underappreciated sources of complexity, including GAPs acting from multiple sites in cells, working with multiple GTPases, and contributing to the spatial and temporal control of regulatory GTPases by serving as both GAPs and effectors.
Identifiants
pubmed: 32614697
doi: 10.1091/mbc.E20-01-0012
pmc: PMC7543072
doi:
Substances chimiques
Cytoskeletal Proteins
0
ELMOD2 protein, mouse
0
GTPase-Activating Proteins
0
Microtubule-Associated Proteins
0
Arl2 protein, mouse
EC 3.6.1.-
GTP-Binding Proteins
EC 3.6.1.-
ADP-Ribosylation Factors
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2070-2091Subventions
Organisme : NCI NIH HHS
ID : F31 CA236493
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS055077
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK064380
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122568
Pays : United States
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