Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 13
pubmed:dateCreated
2005-6-24
pubmed:abstractText
Osteoclast maturation is accompanied by changes in podosome patterning, resulting in the formation of a peripheral belt, which requires an intact microtubule network. Here, we report that by inhibiting Rho, the podosome belt is maintained at the cell periphery despite depolymerisation of microtubules by nocodazole. Rho inhibition was correlated to the increase in microtubule stabilisation and microtubule acetylation. By microinjecting activated Rho or its activated effector mDia2 in osteoclasts, we found that the podosome belt was disrupted and the level of microtubule acetylation dramatically decreased. We further characterised the molecular mechanism responsible for microtubule deacetylation by co-immunoprecipitation experiments. We found that not only was mDia2 coprecipitating with the recently identified microtubule deacetylase HDAC6 but that it also activated the microtubule deacetylase activity of HDAC6 in an in vitro deacetylase assay. Finally, we found that during osteoclastogenesis, there is a correlation between the increase in microtubule acetylation and the podosome belt stabilisation and that if Rho is inhibited in the early stages of osteoclast differentiation, it accelerates both microtubule acetylation and podosome belt stabilisation. Altogether, our data reveal a pathway in which Rho interferes with the osteoclast maturation process by controlling the level of microtubule acetylation and actin organisation through mDIA2 and HDAC6.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2901-11
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts.
pubmed:affiliation
Laboratoire de Biologie Moléculaire et Cellulaire, UMR 5665 CNRS/ENS, INRA 913, Ecole Normale Supérieure de Lyon, 46, allée d'Italie, 69364 Lyon Cedex 7, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't