Characterization of CLP36/Elfin/PDLIM1 in the nervous system.
CLP36, one of the alpha-Actinin Associated LIM Protein (ALP)/Enigma family proteins, has a wide tissue distribution, but little is known about its expression and role in the nervous system. We show here that CLP36 is expressed in sensory ganglia but not in the CNS of adult rats. In primary dorsal root ganglion (DRG) neurons, CLP36 is distributed in the soma and neurites with enrichment in the growth cones. CLP36 forms a complex with alpha-actinin and is localized to actin cytoskeleton. To examine the role of CLP36 in neuronal cells, we transfected PC12 cells with a series of CLP36 deletion mutants and found that over-expression of CLP36 PDZ domain affects neurite outgrowth. Reduction of CLP36 function in PC12 cells by RNA interference (RNAi) induced lamellipodial protrusions around cell periphery and activated growth-cone movements, resulting in an increase in the length and number of neurites. Similarly, inhibition of CLP36 in primary DRG neurons increased the rate of neurite-bearing cells. We also found that CLP36 is up-regulated in DRG neurons and facial motoneurons after nerve injury. These findings suggest that CLP36 serves as a scaffold to form a multiprotein complex that regulates actin cytoskeleton dynamics and plays a role in controlling neurite outgrowth.
Department of Anatomy, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Shizuoka, Japan. kohno@hama-med.ac.jp
Koji
K
Ohno
Hiroshi
H
Kato
Shinji
S
Funahashi
Tomohiko
T
Hasegawa
Kohji
K
Sato
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020220:Facial Nerve Injuries / Q000378:metabolism / Q000473:pathology; D005727:Ganglia, Spinal / Q000166:cytology / Q000473:pathology; D045888:Ganglion Cysts; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D047468:Immunoprecipitation / Q000379:methods; D060588:LIM Domain Proteins; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D020932:Nerve Growth Factor / Q000494:pharmacology; D009420:Nervous System / Q000254:growth & development / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors; D014162:Transfection / Q000379:methods
C484572:LDB2 protein, human; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor