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Negative regulators of a growth factor-mediated signaling pathway in the nematode Caenorhabditis elegans

Citation

Lee, Junho (1994) Negative regulators of a growth factor-mediated signaling pathway in the nematode Caenorhabditis elegans. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/g59t-0b31. https://resolver.caltech.edu/CaltechTHESIS:05092013-145747882

Abstract

Vulval differentiation in C. elegans is mediated by an Epidermal growth factor (EGF)- EGF receptor (EGFR) signaling pathway. I have cloned unc-101, a negative regulator of vulval differentiation of the nematode C. elegans. unc-101 encodes a homolog of AP47, the medium chain of the trans-Golgi clathrin-associated protein complex. This identity was confirmed by cloning and comparing sequence of a C. elegans homolog of AP50, the medium chain of the plasma membrane clathrin-associated protein complex. I provided the first genetic evidence that the trans-Golgi clathrin-coated vesicles are involved in regulation of an EGF signaling pathway. Most of the unc-101 alleles are deletions or nonsense mutations, suggesting that these alleles severely reduce the unc-101 activity. A hybrid gene that contains parts of unc-101 and mouse AP4 7 rescued at least two phenotypes of unc-101 mutations, the Unc and the suppression of vulvaless phenotype of let-23(sy1) mutation. Therefore, the functions of AP47 are conserved between nematodes and mammals.

unc-101 mutations can cause a greater than wild-type vulval differentiation in combination with certain mutations in sli-1, another negative regulator of the vulval induction pathway. A mutation in a new gene, rok-1, causes no defect by itself, but causes a greater than wild-type vulval differentiation in the presence of a sli-1 mutation. The unc-101; rok-1; sli-1 triple mutants display a greater extent of vulval differentiation than any double mutant combinations of unc-101, rok-1 and sli-1. Therefore, rok-1 locus defines another negative regulator of the vulval induction pathway.

I analyzed a second gene encoding an AP47 homolog in C. elegans. This gene, CEAP47, encodes a protein 72% identical to both unc-101 and mammalian AP47. A hybrid gene containing parts of unc-101 and CEAP47 sequences can rescue phenotypes of unc-101 mutants, indicating that UNC- 101 and CEAP47 proteins can be redundant if expressed in the same set of cells.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Biology
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Sternberg, Paul W.
Thesis Committee:
  • Anderson, David J.
  • Dunphy, William G.
  • Meyerowitz, Elliot M.
  • Varshavsky, Alexander J.
Defense Date:1 November 1993
Record Number:CaltechTHESIS:05092013-145747882
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:05092013-145747882
DOI:10.7907/g59t-0b31
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7691
Collection:CaltechTHESIS
Deposited By: Benjamin Perez
Deposited On:09 May 2013 22:15
Last Modified:16 Apr 2021 22:26

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