Physiological functions of glutamine(Q)-rich regions present in yeast endocytic adaptors

Arpita Sen, Purdue University

Abstract

Endocytosis is an essential cellular process with its key players conserved across evolution. However, a few mammalian proteins involved in endocytosis, such as huntingtin, do not seem to have homologs in lower eukaryotes such as budding yeast. Nonetheless, glutamine-rich (QR) regions (analogous to the characteristic huntingtin QR) are present in several yeast endocytic proteins. This led us to speculate that the yet-to-be established physiological function of huntingtin's QR is distributed among these proteins. Therefore, we took advantage of yeast as a model organism to investigate the physiological relevance of QR in endocytosis. Specifically, we tested the hypothesis that QR regions present in yeast endocytic adaptors are involved in specific protein-protein interactions that promote the assembly and function of endocytic sites. We devised a protein-sequence analysis method to determine the boundaries of QR regions and identify neighboring non-Q residues likely to be involved in conferring functional specificity. Furthermore, our results showed that the endocytic adaptor epsin is a valid model of endocytic Q R-containing protein. Here we show that epsin QR sequences enhance recruitment of multiple endocytic proteins [for e.g., of the HIP1 (Huntingtin-Interacting Protein 1) homolog, Sla2] to sites of endocytosis. Furthermore, our results indicate that QR sequences present in epsins, and coiled coil regions contained in Sla2 were important for associating with each other. Importantly, these QR-mediated interactions were relevant not only for supporting the uptake of an epsin-specific cargo that we identified, but also contributed to the signaling functions of epsin in cell division regulation. In this study we propose that certain QR sequences present in yeast endocytic proteins bear a strong coiled-coil (CC) forming propensity whereby they provide functional platforms for protein interactions and lead to assembly and/ or consolidation of endocytic sites. This research is highly relevant to advance our understanding of the mechanisms of loss-of-function effects due to QR-expansion causative of neurodegenerative illnesses such as Huntington's disease.

Degree

Ph.D.

Advisors

Aguilar, Purdue University.

Subject Area

Genetics|Cellular biology|Biochemistry

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