Actin-related protein 6 facilitates proneural protein-induced gene activation for rapid neural differentiation.

Neurogenesis is initiated by basic helix-loop-helix proneural proteins. Here, we show that Actin-related protein 6 (Arp6), a core component of the H2A.Z exchange complex SWR1, interacts with proneural proteins and is crucial for efficient onset of proneural protein target gene expression.

Proneural proteins Achaete and Scute associate with nuclear actin to promote formation of external sensory organs.

Basic helix-loop-helix (bHLH) proneural proteins promote neurogenesis through transcriptional regulation. Although much is known about the tissue-specific regulation of proneural gene expression, how proneural proteins interact with transcriptional machinery to activate downstream target genes is less clear. Drosophila proneural proteins Achaete (Ac) and Scute (Sc) induce external sensory organ formation by activating neural precursor gene expression.

Negative-feedback regulation of proneural proteins controls the timing of neural precursor division.

Neurogenesis requires precise control of cell specification and division. In Drosophila, the timing of cell division of the sensory organ precursor (SOP) is under strict temporal control. But how the timing of mitotic entry is determined remains poorly understood.

Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle-associated protein astrin.

Emerging evidence shows that glycogen synthase kinase 3beta (GSK3beta) is involved in mitotic division and that inhibiting of GSK3beta kinase activity causes defects in spindle microtubule length and chromosome alignment. However, the purpose of GSK3beta involvement in spindle microtubule assembly and accurate chromosome segregation remains obscure. Here, we report that GSK3beta interacts with the spindle-associated protein Astrin both in vitro and in vivo.

hNinein is required for targeting spindle-associated protein Astrin to the centrosome during the S and G2 phases.

Human Ninein (hNinein) is implicated in centrosomal microtubule nucleation and microtubule anchoring in interphase cells and may act as a scaffold protein, but its direct interaction partners remain unexplored in the centrosome. In this report, we show clearly that a spindle-associated protein, Astrin, interacts and co-localizes with hNinein at the centrosome during the S and G2 phases, and this complex may dissociate in the M phase. We also demonstrate that the truncated forms of hNinein, which could interfere with gamma-tubulin and function as dominant-negative mutants, are able to affect Astrin localization to the centrosome.

GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a negative regulator of GSK3beta.

Although prominent FRAT/GBP exhibits a limited degree of homology to Axin, the binding sites on GSK3 for FRAT/GBP and Axin may overlap to prevent the effect of FRAT/GBP in stabilizing beta-catenin in the Wnt pathway. Using a yeast two-hybrid screen, we identified a novel protein, GSK3beta interaction protein (GSKIP), which binds to GSK3beta. We have defined a 25-amino acid region in the C-terminus of GSKIP that is highly similar to the GSK3beta interaction domain (GID) of Axin.