LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome.
Williams Syndrome is a developmental disorder that is characterized by cardiovascular problems, particular facial features and several typical behavioral and neurological abnormalities. In Williams Syndrome patients, a heterozygous deletion is present of a region on chromosome 7q11.23 (the Williams Syndrome critical region), which spans approximately 20 genes. Two of these genes encode proteins that regulate dynamic aspects of the cytoskeleton of the cell, either via the actin filament system (LIM kinase 1, or LIMK1), or through the microtubule network (cytoplasmic linker protein of 115 kDa, or CLIP-115). The recent findings that knockout mice lacking LIMK1 or CLIP-115 have distinct neurological and behavioural phenotypes, indicates that cytoskeletal defects might play a role in the development of neurological symptoms in Williams Syndrome patients. In this review, we discuss the properties of LIMK and CLIP family proteins, their function in the regulation of the actin and microtubule cytoskeletal systems, respectively, and the relationship with neurodevelopmental aspects of Williams Syndrome.
Hoogenraad
Casper C
CC
Department of Neuroscience, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands. c.hoogenraad@erasmusmc.nl
Akhmanova
Anna
A
Galjart
Niels
N
De Zeeuw
Chris I
CI
D000199:Actins / Q000378:metabolism; D000818:Animals; D002897:Chromosomes, Human, Pair 7; D003599:Cytoskeleton / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000072159:Dynactin Complex; D006801:Humans; D054461:Lim Kinases; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018980:Williams Syndrome / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D004268:DNA-Binding Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C109878:cytoplasmic linker protein 115; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D017346:Protein Serine-Threonine Kinases