Bialas, Chris
(2010)
Signaling Pathways that Regulate Autophagic Muscle Protein Degradation in C. elegans.
Undergraduate Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Protein degradation in C. elegans muscle cells is very tightly controlled by opposing signaling cascades. Excessive FGFR, low IGFR or TGF-B signaling, starvation or denervation all lead to muscle protein breakdown. Here we show that under conditions of activated FGFR, low IGFR or low TGF-B activity or mutationally hyperactived MAP kinase, soluble protein in muscle cytosol is degraded through autophagy. Degradation under these conditions is prevented by a reduction of function mutation in unc-51 (encodes Atg1 homologue), by RNAi knockdown of BEC-1 (beclin), or ATG-7 (Atg7 homologue) or by treatment with N6,N6-dimethyladenosine, a presumed inhibitor of type III PtdIns-3-kinase. We infer that the MAP kinase cascade positively regulates autophagy when the FGFR signal is too high or the IGFR signal too low . However, we have yet to identify how a MAPK signal plays into TGF-B regulation of autophagy. Protein degradation following starvation or disruption of cholinergic signaling (ACh-deficient cha-1 mutant) is not prevented by interference with autophagy, consistent with the known sensitivity to proteasome inhibitors. We have also implicated the signaling protein RSK as necessary for autophagic signaling either in parallel with or downstream of MAPK The metabolic reserve of protein in muscle can be mobilized by catabolism in response to failure of any one of a variety of signals of 'healthy' conditions. To achieve versatility and flexibility of response, muscle cells evidently use multiple proteolytic systems and regulate them independently by integrating more than one regulatory input to each degradation system.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
13 May 2010 |
| Date Type: |
Completion |
| Defense Date: |
10 April 2010 |
| Approval Date: |
13 May 2010 |
| Submission Date: |
29 April 2010 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences
David C. Frederick Honors College |
| Degree: |
BPhil - Bachelor of Philosophy |
| Thesis Type: |
Undergraduate Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
atrophy; FGF; FGFR; IGF; IGFR; LacZ; MAPK; proteolysis; RNAi; TGF-B; worms |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-04292010-130408/, etd-04292010-130408 |
| Date Deposited: |
10 Nov 2011 19:43 |
| Last Modified: |
15 Nov 2016 13:42 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/7730 |
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