Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.

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 i...

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Autores principales:	Raphael Trefzer, Orly Elpeleg, Tatyana Gabrusskaya, Polina Stepensky, Hagar Mor-Shaked, Robert Grosse, Dominique T Brandt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b2fe302d8c54a67a7cd3f72f09ac832
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spelling	oai:doaj.org-article:4b2fe302d8c54a67a7cd3f72f09ac8322021-12-02T20:11:14ZCharacterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.1932-620310.1371/journal.pone.0252428https://doaj.org/article/4b2fe302d8c54a67a7cd3f72f09ac8322021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252428https://doaj.org/toc/1932-6203Diaphanous 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.Raphael TrefzerOrly ElpelegTatyana GabrusskayaPolina StepenskyHagar Mor-ShakedRobert GrosseDominique T BrandtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252428 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raphael Trefzer Orly Elpeleg Tatyana Gabrusskaya Polina Stepensky Hagar Mor-Shaked Robert Grosse Dominique T Brandt Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.
description	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.
format	article
author	Raphael Trefzer Orly Elpeleg Tatyana Gabrusskaya Polina Stepensky Hagar Mor-Shaked Robert Grosse Dominique T Brandt
author_facet	Raphael Trefzer Orly Elpeleg Tatyana Gabrusskaya Polina Stepensky Hagar Mor-Shaked Robert Grosse Dominique T Brandt
author_sort	Raphael Trefzer
title	Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.
title_short	Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.
title_full	Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.
title_fullStr	Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.
title_full_unstemmed	Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.
title_sort	characterization of a l136p mutation in formin-like 2 (fmnl2) from a patient with chronic inflammatory bowel disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4b2fe302d8c54a67a7cd3f72f09ac832
work_keys_str_mv	AT raphaeltrefzer characterizationofal136pmutationinforminlike2fmnl2fromapatientwithchronicinflammatoryboweldisease AT orlyelpeleg characterizationofal136pmutationinforminlike2fmnl2fromapatientwithchronicinflammatoryboweldisease AT tatyanagabrusskaya characterizationofal136pmutationinforminlike2fmnl2fromapatientwithchronicinflammatoryboweldisease AT polinastepensky characterizationofal136pmutationinforminlike2fmnl2fromapatientwithchronicinflammatoryboweldisease AT hagarmorshaked characterizationofal136pmutationinforminlike2fmnl2fromapatientwithchronicinflammatoryboweldisease AT robertgrosse characterizationofal136pmutationinforminlike2fmnl2fromapatientwithchronicinflammatoryboweldisease AT dominiquetbrandt characterizationofal136pmutationinforminlike2fmnl2fromapatientwithchronicinflammatoryboweldisease
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Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease.

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