LIMK1 acts downstream of BMP signaling in developing retinal ganglion cell axons but not dendrites.
The actin cytoskeleton inside extending axonal and dendritic processes must undergo continuous assembly and disassembly. Some extrinsic factors modulate actin turnover through controlling the activity of LIM kinase 1 (LIMK1), which phosphorylates and inactivates the actin depolymerizing factor cofilin. Here, we for the first time examine the function and regulation of LIMK1 in vivo in the vertebrate nervous system. Upon expression of wildtype or kinase-dead forms of the protein, dendrite growth by Xenopus retinal ganglion cells (RGCs) was unchanged. In contrast, maintaining a low, but significant level, of LIMK1 function in the RGC axon is critical for proper extension. Interestingly, bone morphogenetic protein receptor II (BMPRII) is a major regulator of LIMK1 in extending RGC axons, as expression of a BMPRII lacking the LIMK1 binding region caused a dramatic shortening of the axons. Previously, we found that BMPRIIs stimulate dendrite initiation in vivo. Thus, the fact that manipulation of LIMK1 activity failed to alter dendrite growth suggests that BMPs may activate distinct signalling pathways in axons and dendrites.
Hocking
Jennifer C
JC
Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Hehr
Carrie L
CL
Bertolesi
Gabriel
G
Funakoshi
Hiroshi
H
Nakamura
Toshikazu
T
McFarlane
Sarah
S
D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017931:DNA Primers; D003712:Dendrites / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019076:Transgenes; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D029867:Xenopus Proteins