Rab27A Regulates Transport of Cell Surface Receptors Modulating Multinucleation and Lysosome-Related Organelles in Osteoclasts

Megumi Shimada-Sugawara, Eiko Sakai, Kuniaki Okamoto, Mitsunori Fukuda, Tetsuro Izumi, Noriaki Yoshida, Takayuki Tsukuba

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Rab27A regulates transport of lysosome-related organelles (LROs) and release of secretory granules in various types of cells. 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 ashen 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 ashen BMMs than in wild-type BMMs. The cell surface level of c-fms, an M-CSF receptor, was slightly higher in ashen BMMs than in wild-type BMMs, and down-regulation of RANK, a RANKL receptor, was delayed. In addition to receptors, OCLs derived from ashen 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.

Original languageEnglish
Article number9620
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015
Externally publishedYes

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Cell Surface Receptors
Osteoclasts
Lysosomes
Organelles
Macrophages
Bone Marrow
Macrophage Colony-Stimulating Factor Receptors
RANK Ligand
Proto-Oncogene Proteins
Lysosome-Associated Membrane Glycoproteins
Cathepsin K
Somatostatin-Secreting Cells
Extracellular Signal-Regulated MAP Kinases
Secretory Vesicles
Giant Cells
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Protein-Tyrosine Kinases
Small Interfering RNA
Actins

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Rab27A Regulates Transport of Cell Surface Receptors Modulating Multinucleation and Lysosome-Related Organelles in Osteoclasts. / Shimada-Sugawara, Megumi; Sakai, Eiko; Okamoto, Kuniaki; Fukuda, Mitsunori; Izumi, Tetsuro; Yoshida, Noriaki; Tsukuba, Takayuki.

In: Scientific Reports, Vol. 5, 9620, 2015.

Research output: Contribution to journalArticle

Shimada-Sugawara, Megumi ; Sakai, Eiko ; Okamoto, Kuniaki ; Fukuda, Mitsunori ; Izumi, Tetsuro ; Yoshida, Noriaki ; Tsukuba, Takayuki. / Rab27A Regulates Transport of Cell Surface Receptors Modulating Multinucleation and Lysosome-Related Organelles in Osteoclasts. In: Scientific Reports. 2015 ; Vol. 5.
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