Williams-Beuren syndrome (WBS) or Williams syndrome (WS) results from the hemizygous deletion of 1.5 to 1.8 Mb on chromosome 7q11.23 which contains approximately 28 genes; it is inherited as an autosomal dominant. The gene LIMK1 is within the deleted interval; the contribution of reduced dosage of LIMK1 to the WBS phenotypes is not clear (see Genetics section of Disease Summary information, below).
LIMK1 is a serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. There is a single fly ortholog, Dmel\LIMK1, for which for which classical hypomorphic alleles, temperature-sensitive alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\LIMK1 is also orthologous to a second human gene, LIMK2.
The human LIMK1 gene has not been introduced into flies.
A loss-of-function mutation of Dmel\LIMK1 exhibits defects in learning, locomotor, and courtship behaviors, phenotypes which share aspects of the phenotypes of Williams-Beuren syndrome. Genetic and physical interactions of Dmel\LIMK1 have been characterized; see below and in the gene report for Dmel\LIMK1.
[updated Nov. 2016 by FlyBase; FBrf0222196]
LIMK1 hemizygosity has been implicated in the impaired visuospatial constructive cognition of Williams-Beuren syndrome (pubmed:8689688), but this claim has been called into question (pubmed:9915950). More recent work leads to the conclusion that the deletion of one copy of LIMK1 alone is not sufficient to result in spatial impairment, but leaves open the possibility that LIMK1 contributes to the WBS cognitive deficits if deleted in combination with other genes within the WBS deletion (pubmed:16216290).
LIMK1 is a serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIMK1 and LIMK2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. LIMK1 regulates actin polymerization via phosphorylation and inactivation of the actin binding factor cofilin. [from Gene Cards, LIMK2; 2016.11.29]
One to one: 1 human to 1 Drosophila.
Ortholog of human LIMK1 gene (1 Drosophila to 1 human). Over its amino portion (~700aa), Dmel\LIMK1 shares 43% identity and 56% similarity with human LIMK1; in insects this protein extends an additional ~500 amino acids (no protein domain identified) relative to the gene in vertebrates.
