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Here, we identified up-regulation of Rab27A during differentiation of osteoclasts (OCLs) from bone-marrow macrophages (BMMs), by DNA microarray analysis. Rab27A deficiency in OCLs, using small interfering RNA (siRNA) knockdown in RAW-D cell line or BMMs derived from <jats:italic>ashen<\/jats:italic> mice, which display genetic defects in Rab27A expression, induced multinucleated and giant cells. Upon stimulation with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL), essential cytokines for OCL differentiation, phosphorylation levels of extracellular signal-regulated kinase (Erk), proto-oncogene tyrosine-protein kinase (Src) and p-38 were slightly enhanced in <jats:italic>ashen<\/jats:italic> BMMs than in wild-type BMMs. The cell surface level of c-fms, an M-CSF receptor, was slightly higher in <jats:italic>ashen<\/jats:italic> BMMs than in wild-type BMMs and down-regulation of RANK, a RANKL receptor, was delayed. In addition to receptors, OCLs derived from <jats:italic>ashen<\/jats:italic> mice exhibited aberrant actin ring formation, abnormal subcellular localization of lysosome-associated membrane protein (LAMP2) and cathepsin K (CTSK) and marked reduction in resorbing activity. Thus, these findings suggest that Rab27A regulates normal transport of cell surface receptors modulating multinucleation and LROs in OCLs.<\/jats:p>","DOI":"10.1038\/srep09620","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T09:39:40Z","timestamp":1429263580000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Rab27A Regulates Transport of Cell Surface Receptors Modulating Multinucleation and Lysosome-Related Organelles in Osteoclasts"],"prefix":"10.1038","volume":"5","author":[{"given":"Megumi","family":"Shimada-Sugawara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiko","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniaki","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsunori","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Izumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Tsukuba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,4,16]]},"reference":[{"key":"BFsrep09620_CR1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nrm2728","volume":"10","author":"H Stenmark","year":"2009","unstructured":"Stenmark, H. 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