Student Theses and Dissertations

Author

Wendy Wang

Date of Award

2018

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Shaham Laboratory

Abstract

Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized extracellular space, or compartment, important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. Sensory organ glia are conserved across organisms, but our current understanding of how they form sensory compartments is generally lacking. To date, the Caenorhabditis elegans amphid sensory organ has provided critical insight into some of these developmental processes. DAF-6, a Patched-related protein, was previously shown to be required in amphid glia to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion. My work here further explores the machinery underlying compartment size control. In seeking genes whose inactivation restores normal compartment size to daf-6 mutants, I identify two novel regulators: IGDB-2, an Ig/FNIII protein, and LGC-34, a ligand-gated ion channel. First, igdb-2 mutations suppress daf-6 mutant defects. IGDB-2 acts in glia, where it localizes to glial membranes surrounding NREs, and, together with LIT-1 and SNX-1, regulates compartment morphogenesis. Second, immunoprecipitation followed by mass spectrometry demonstrates that IGDB-2 binds to LGC-34, and lgc-34 mutations inhibit igdb-2 suppression of daf-6. My findings thus reveal the novel IGDB-2/LGC-34 membrane protein complex and suggest new molecular mechanisms for how sensory compartment size is controlled.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

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Life Sciences Commons

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