Genetic analysis of protein kinase C and MAPK in Caenorhabditis elegans mechanosensation
By: by Rhonda Hyde
Published: 2008
Language: eng
Number of pages: 177
Description: The molecular mechanisms underlying mechanosensation are poorly understood. To find genes that are involved in mechanosensation, we cloned and characterized a mutation that affected nose touch responses in the nematode C. elegans . This mutation corresponded to an amino acid change in PKC-1. pkc-1 can act in sensory neurons and interneurons for normal responses. By selectively removing pkc-1 function in the interneurons, we found that pkc-1 is required in these cells for normal mechanosensory response. This is a new site of action for pkc-1 in C. elegans . Protein kinase Cs are a family of serine/threonine kinases that can be divided into three subtypes: conventional, novel and atypical. PKC-1 is a member of the novel class. As loss of PKC-1 did not completely abolish nose touch response, we wondered whether other C. elegans PKCs function with pkc-1 . We systematically made and tested loss of function combinations for all available PKC alleles and found that tpa-1 , the other novel PKC, acts partially redundantly with pkc-1 for nose touch. This indicates that pkc-1 functions with tpa-1 for normal mechanosensory response.

To understand the context by which pkc-1 acts, we undertook a literature-based search to identify known PKC phosphorylation targets in other organisms. We then tested the C. elegans homologs with known nervous system expression to determine whether these proteins act in nose touch response. This strategy led to the identification of the ERK MAPK signaling pathway. Loss of pathway components LIN-45 Raf and MPK-1 ERK resulted in nose touch defects similar to PKC-1 loss. Like PKC-1, LIN-45 is required in the interneurons for normal touch response. Lastly, the effects of losing both PKC-1 and LIN-45 were not additive. This suggests that these two proteins function in the same pathway and is consistent with the previous link between PKC and Raf in other systems. This is one of the first studies highlighting the in vivo relevance of PKC and ERK interactions. These results provide valuable clues as to the function of individual PKC enzymes in biological functions as well as molecular mechanisms underlying sensory transduction.
Notes: "September 2008."

Thesis (Ph.D., Division of Medical Sciences (Neurobiology))--Harvard University, 2008.

Includes bibliographical references.