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

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.

Základní údaje

Originální název

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

Autoři

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

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.393

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1093/hmg/ddu186

UT WoS

000340238200015

Klíčová slova anglicky

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

Štítky

kontrola MP, MP, neMU

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 2. 2015 08:33, Martina Prášilová

Anotace

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.

Citovat

HU, J.J., J. LU, G.W. LIAN, R.J. FERLAND, Markus DETTENHOFER a V.L. SHEEN. Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate. Human molecular genetics. OXFORD: OXFORD UNIV PRESS, 2014, roč. 23, č. 17, s. 4663-4673. ISSN 0964-6906. Dostupné z: https://dx.doi.org/10.1093/hmg/ddu186.

@article{1227833,
   author = {Hu, J.J. and Lu, J. and Lian, G.W. and Ferland, R.J. and Dettenhofer, Markus and Sheen, V.L.},
   article_location = {OXFORD},
   article_number = {17},
   doi = {http://dx.doi.org/10.1093/hmg/ddu186},
   keywords = {CELL-MIGRATION; ADHESION DYNAMICS; ACTIN; MUTATIONS; FLNB; CARTILAGE; GENE; PHOSPHORYLATION; CHONDROGENESIS; DISRUPTION},
   language = {eng},
   issn = {0964-6906},
   journal = {Human molecular genetics},
   title = {Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate},
   url = {http://hmg.oxfordjournals.org/content/23/17/4663.long},
   volume = {23},
   year = {2014}
}

TY  - JOUR
ID  - 1227833
AU  - Hu, J.J. - Lu, J. - Lian, G.W. - Ferland, R.J. - Dettenhofer, Markus - Sheen, V.L.
PY  - 2014
TI  - Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate
JF  - Human molecular genetics
VL  - 23
IS  - 17
SP  - 4663-4673
EP  - 4663-4673
PB  - OXFORD UNIV PRESS
SN  - 09646906
KW  - CELL-MIGRATION
KW  - ADHESION DYNAMICS
KW  - ACTIN
KW  - MUTATIONS
KW  - FLNB
KW  - CARTILAGE
KW  - GENE
KW  - PHOSPHORYLATION
KW  - CHONDROGENESIS
KW  - DISRUPTION
UR  - http://hmg.oxfordjournals.org/content/23/17/4663.long
L2  - http://hmg.oxfordjournals.org/content/23/17/4663.long
N2  - 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.
ER  -

HU, J.J., J. LU, G.W. LIAN, R.J. FERLAND, Markus DETTENHOFER a V.L. SHEEN. Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate. \textit{Human molecular genetics}. OXFORD: OXFORD UNIV PRESS, 2014, roč.~23, č.~17, s.~4663-4673. ISSN~0964-6906. Dostupné z: https://dx.doi.org/10.1093/hmg/ddu186.

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