Goldberg-Shprintzen disease (GOSHS) is a rare
microcephaly syndrome accompanied by
intellectual disability, dysmorphic facial features,
peripheral neuropathy and
Hirschsprung disease. It is associated with recessive mutations in the gene encoding
kinesin family member 1-binding
protein (KIF1BP, also known as KIFBP). The encoded
protein regulates axon microtubules dynamics,
kinesin attachment and mitochondrial biogenesis, but it is not clear how its loss could lead to
microcephaly. We identified KIF1BP in the interactome of
citron kinase (CITK, also known as
CIT), a
protein produced by the primary hereditary
microcephaly 17 (MCPH17) gene. KIF1BP and CITK interact under physiological conditions in mitotic cells. Similar to CITK, KIF1BP is enriched at the midbody ring and is required for cytokinesis. The association between KIF1BP and CITK can be influenced by CITK activity, and the two
proteins may antagonize each other for their midbody localization. KIF1BP knockdown decreases microtubule stability, increases KIF23 midbody levels and impairs midbody localization of KIF14, as well as of chromosome passenger complex. These data indicate that KIF1BP is a CITK interactor involved in midbody maturation and abscission, and suggest that cytokinesis failure may contribute to the
microcephaly phenotype observed in GOSHS.