The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase.
The majority of excitatory synaptic transmission in the brain occurs at dendritic spines, which are actin-rich protrusions on the dendrites. The asymmetric nature of these structures suggests that proteins regulating cell polarity might be involved in their formation. Indeed, the polarity protein PAR-3 is required for normal spine morphogenesis. However, this function is independent of association with atypical protein kinase C (aPKC) and PAR-6. Here we show that PAR-6 together with aPKC plays a distinct but essential role in spine morphogenesis. Knockdown of PAR-6 inhibits spine morphogenesis, whereas overexpression of PAR-6 increases spine density, and these effects are mediated by aPKC. Using a FRET biosensor, we further show that p190 RhoGAP and RhoA act downstream of the PAR-6/aPKC complex. These results define a role for PAR-6 and aPKC in dendritic spine biogenesis and maintenance, and reveal an unexpected link between the PAR-6/aPKC complex and RhoA activity.
Zhang
Huaye
H
Department of Microbiology and Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. hz5a@virginia.edu
Macara
Ian G
IG
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D016764:Cell Polarity; D004268:DNA-Binding Proteins / Q000378:metabolism*; D049229:Dendritic Spines / Q000201:enzymology*; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099221:Protein Kinase C zeta
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011493:Protein Kinase C; D012097:Repressor Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000099221:Protein Kinase C zeta; C513040:Arhgap35 protein, rat; C504908:Pard6a protein, rat; C115015:PKC-3 protein