J 2014

Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate

HU, J.J., J. LU, G.W. LIAN, R.J. FERLAND, Markus DETTENHOFER et. al.

Basic information

Original name

Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate

Authors

HU, J.J., J. LU, G.W. LIAN, R.J. FERLAND, Markus DETTENHOFER and V.L. SHEEN

Edition

Human molecular genetics, OXFORD, OXFORD UNIV PRESS, 2014, 0964-6906

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 6.393

Organization unit

Central European Institute of Technology

DOI

UT WoS

000340238200015

Keywords in English

CELL-MIGRATION; ADHESION DYNAMICS; ACTIN; MUTATIONS; FLNB; CARTILAGE; GENE; PHOSPHORYLATION; CHONDROGENESIS; DISRUPTION

Tags

Tags

International impact, Reviewed
Změněno: 27/2/2015 08:33, Martina Prášilová

Abstract

V originále

Filamin B (FlnB) is an actin-binding protein thought to transduce signals from various membrane receptors and intracellular proteins onto the actin cytoskeleton. Formin1 (Fmn1) is an actin-nucleating protein, implicated in actin assembly and intracellular signaling. Human mutations in FLNB cause several skeletal disorders associated with dwarfism and early bone fusion. Mouse mutations in Fmn1 cause aberrant fusion of carpal digits. We report here that FlnB and Fmn1 physically interact, are co-expressed in chondrocytes in the growth plate and share overlapping expression in the cell cytoplasm and nucleus. Loss of FlnB leads to a dramatic decrease in Fmn1 expression at the hypertrophic-to-ossification border. Loss of Fmn1-FlnB in mice leads to a more severe reduction in body size, weight and growth plate length, than observed in mice following knockout of either gene alone. Shortening of the long bone is associated with a decrease in chondrocyte proliferation and an overall delay in ossification in the double-knockout mice. In contrast to FlnB null, Fmn1 loss results in a decrease in the width of the prehypertrophic zone. Loss of both proteins, however, causes an overall decrease in the width of the proliferation zone and an increase in the differentiated hypertrophic zone. The current findings suggest that Fmn1 and FlnB have shared and independent functions. FlnB loss promotes prehypertrophic differentiation whereas Fmn1 leads to a delay. Both proteins, however, regulate chondrocyte proliferation, and FlnB may regulate Fmn1 function at the hypertrophic-to-ossification border, thereby explaining the overall delay in ossification.