title: Microtubule-associated protein light chain 3 regulates Cdc42-dependent actin ring formation in osteoclast.
abstract: Microtubule-associated protein 1 light chain-3 (LC3) plays a critical role in autophagosome formation during autophagy; however, its potential alternative functions remain largely unexplored. Here we demonstrate a discrete role for LC3 in osteoclast, a specialized bone-resorbing cell that requires a dynamic microtubule network for its activity. We found that an increase in the conversion of soluble LC3-I to lipid-bound LC3-II in mature osteoclast was correlated with osteoclast activity, but not with autophagic activity. Knockdown of LC3 using small interfering RNA did not affect TRAP-positive multinucleated cell formation, but suppressed actin ring formation, cathepsin K release, and the subsequent bone-resorbing capacity of osteoclasts. LC3 mediated this function by associating with microtubules and regulating Cdc42 activity. More importantly, LC3-II protein levels were reduced by the Atg5 knockdown, and this knockdown led to decrease in Cdc42 activity, indicating that LC3-II is critical for Cdc42 activity. Overexpression of a constitutively active form of Cdc42 partially rescued the phenotype induced by LC3 knockdown. Our results demonstrate that LC3 contributes to the regulatory link between the microtubule and Cdc42 involved in bone-resorbing activity, providing evidence for a role for LC3 in mediating diverse cellular functions beyond its role as an autophagy protein.
authors.affiliation: Department of Medicine, Graduate School, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Chung
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
authors.forename: Bongkun
authors.initials: B
authors.lastname: Choi
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Sohn
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Yoon
authors.forename: Wan-Jong
authors.initials: WJ
authors.lastname: Kim
authors.forename: Dong-Hou
authors.initials: DH
authors.lastname: Kim
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
mesh_terms: D000818:Animals; D056657:Cathepsin K / Q000378:metabolism; D002454:Cell Differentiation; D055785:Gene Knockdown Techniques; D006801:Humans; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*
chemical_list: D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D056657:Cathepsin K; D020764:cdc42 GTP-Binding Protein