The function of GAK family proteins in Notch signaling pathway

Ting Bai, Purdue University

Abstract

Ligand endocytosis is a key event in the activation of the Notch pathway, a conserved signaling module that plays diverse roles during animal development. Using Drosophila, we have shown that J-domain-containing protein auxilin participates in the Notch pathway by facilitating Delta endocytosis. Since there are multiple endocytic pathways in higher eukaryotes, it is unclear if the auxilin-dependent pathway is also important in Notch signaling in other animal systems. To address this issue, we studied the developmental functions of auxilin orthologs in zebrafish. Unlike Drosophila, zebrafish contains two auxilin-like proteins, auxilin and GAK (hereafter referred to as zAux and zGAK respectively), differing in their domain structures and expression patterns. Expression of either zGAK or zAux in flies can rescue the phenotypes of Drosophila auxilin (dAux) mutants, suggesting that they are at least partially functionally redundant. Down-regulation of zGAK alone could increase the number of neural progenitor cells and alter the expression of some well-known Notch target genes. Taken together, these results suggest that a requirement of GAK protein function in the Notch pathway during neurogenesis is evolutionally conserved. Surprisingly, at later stages of development, inhibition of zGAK function causes increased apoptotic cell death in neural tissues of zebrafish embryos, revealing a novel role of GAK in maintaining neuronal survival later during development.

Degree

Ph.D.

Advisors

Chang, Purdue University.

Subject Area

Genetics|Cellular biology

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