UC San Diego

The microtubule (MT) arrays in mature polarized cells comprise mostly of non-centrosomal MTs; their regulation is poorly understood. Recently, the MT minus end binding proteins CAMSAPs have been shown to be important regulators of non-centrosomal microtubule organization and dynamics. In this dissertation I describe my work on the C. elegans member of the CAMSAP family, PTRN-1, and its roles in the injury responses of two types of tissues, the neurons and the epidermis. First, I found that PTRN-1 is required for axon regeneration. Though PTRN-1 is largely dispensable for normal neuronal development, its proper regulation of neuronal microtubule dynamics is required for axons to regrow after injury. The second part of my work focuses on PTRN-1’s role in epidermal development and wound response by regulating epidermal microtubule stability. Mutations in the gene death associated protein kinase 1 (DAPK1)/dapk-1 results in both hyperactive innate immune response and enhanced wound closure in the epidermis. A genetic suppressor screen of the dapk-1 mutant identified PTRN-1 as a key player in dapk-1 mediated wound phenotypes. Further work uncovered DAPK-1 as a potential novel regulator of PTRN-1’s function in epidermal MT architecture and dynamics. My thesis work reveals new in vivo roles of PTRN-1 in regulating non-centrosomal MTs for normal tissue damage response.