Optogenetic activation of Plexin-B1 reveals contact repulsion between osteoclasts and osteoblasts

被引：34

作者：

Roy, Abhijit Deb ^{[1
]}

Yin, Taofei ^{[1
]}

Choudhary, Shilpa ^{[2
]}

Rodionov, Vladimir ^{[1
,3
]}

Pilbeam, Carol C. ^{[2
]}

Wu, Yi I. ^{[1
,4
]}

机构：

[1] Univ Connecticut, Richard D Berlin Ctr Cell Anal & Modeling, Sch Med, 400 Farmington Ave, Farmington, CT 06030 USA

[2] Univ Connecticut, New England Musculoskeletal Inst, Sch Med, Farmington, CT 06030 USA

[3] Univ Connecticut, Dept Cell Biol, Sch Med, Farmington, CT 06030 USA

[4] Univ Connecticut, Dept Genet & Genome Sci, Sch Med, Farmington, CT 06030 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

NUCLEOTIDE EXCHANGE FACTOR; R-RAS; SEMAPHORIN; 4D; BETA-PIX; HIPPOCAMPAL-NEURONS; ACTIN CYTOSKELETON; RECEPTOR PLEXIN-B1; PROTEIN-ACTIVITY; STRUCTURAL BASIS; MAMMALIAN-CELLS;

D O I：

10.1038/ncomms15831

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away. These morphological changes are accompanied by reorganization of Myosin II, PIP3, adhesion and active Cdc42. We attribute the resultant repolarization to RhoA/ROCK-mediated redistribution of beta-Pix, which activates Cdc42 and promotes protrusion. Thus, our data demonstrate a causal role of Plexin-B1 for CIL in osteoblasts and reveals a previously unknown effect of Semaphorin signalling on spatial distribution of an activator of cell migration.

引用

页数：15

共 70 条

[1] OBSERVATIONS ON THE SOCIAL BEHAVIOUR OF CELLS IN TISSUE CULTURE .1. SPEED OF MOVEMENT OF CHICK HEART FIBROBLASTS IN RELATION TO THEIR MUTUAL CONTACTS [J].