In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 5 ( 2021-5-27), p. e0252428-
Abstract:
Diaphanous related formins are highly conserved proteins regulated by Rho-GTPases that act as actin nucleation and assembly factors. Here we report the functional characterization of a non-inherited heterozygous FMNL2 p.L136P mutation carried by a patient who presented with severe very early onset inflammatory bowel disease (IBD). We found that the FMNL2 L136P protein displayed subcellular mislocalization and deregulated protein autoinhibition indicating gain-of-function mechanism. Expression of FMNL2 L136P impaired cell spreading as well as filopodia formation. THP-1 macrophages expressing FMNL2 L136P revealed dysregulated podosome formation and a defect in matrix degradation. Our data indicate that the L136P mutation affects cellular actin dynamics in fibroblasts and immune cells such as macrophages.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0252428
DOI:
10.1371/journal.pone.0252428.g001
DOI:
10.1371/journal.pone.0252428.g002
DOI:
10.1371/journal.pone.0252428.g003
DOI:
10.1371/journal.pone.0252428.g004
DOI:
10.1371/journal.pone.0252428.g005
DOI:
10.1371/journal.pone.0252428.s001
DOI:
10.1371/journal.pone.0252428.s002
DOI:
10.1371/journal.pone.0252428.s003
DOI:
10.1371/journal.pone.0252428.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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