The Rho-specific GEF Lfc interacts with neurabin and spinophilin to regulate dendritic spine morphology.
Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. A yeast two-hybrid analysis using the coiled-coil domain of neurabin revealed an interaction with Lfc, a Rho GEF. Lfc was highly expressed in brain, where it interacted with either neurabin or spinophilin. In neurons, Lfc was largely found in the shaft of dendrites in association with microtubules but translocated to spines upon neuronal stimulation. Moreover, expression of Lfc resulted in reduction in spine length and size. Both the translocation and the effect on spine morphology depended on the coiled-coil domain of Lfc. Coexpression of neurabin or spinophilin with Lfc resulted in their clustering together with F-actin, a process that depended on Rho activity. Thus, interaction between Lfc and neurabin/spinophilin selectively regulates Rho-dependent organization of F-actin in spines and is a link between the microtubule and F-actin cytoskeletons in dendrites.
Ryan
Xiaozhou P
XP
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Alldritt
Jacqueline
J
Svenningsson
Per
P
Allen
Patrick B
PB
Wu
Gang-Yi
GY
Nairn
Angus C
AC
Greengard
Paul
P
D000199:Actins / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001923:Brain Chemistry; D002232:Carbocyanines; D004396:Coloring Agents; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003712:Dendrites / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D010590:Phalloidine; D051381:Rats; D014162:Transfection; D000099273:Neurabins
D000199:Actins; D002232:Carbocyanines; D004396:Coloring Agents; D018076:DNA, Complementary; D020662:Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010590:Phalloidine; D000099273:Neurabins; C024286:3,3'-dioctadecylindocarbocyanine