Publication:
PROTEIN TRAFFICKING IN THE ENDOPLASMIC RETICULUM MEDIATED BY A TPR-CONTAINING ADAPTER PROTEIN

dc.contributor.advisorDaniel N Hebert
dc.contributor.authorCanniff, Nathan P
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.date2024-03-27T20:11:08.000
dc.date.accessioned2024-04-26T16:03:06Z
dc.date.available2024-04-26T16:03:06Z
dc.date.submittedSeptember
dc.date.submitted2023
dc.description.abstractThe endoplasmic reticulum (ER) is a large, multifunctional organelle that acts as the entrance into the secretory pathway, which accounts for the folding and maturation of approximately one third of the human proteome. It is the largest organelle in most cell types and is comprised of a single lumen and a contiguous membrane. The ER is responsible for a multitude of roles including protein translocation, folding, maturation, quality control, and glycosylation to name a few. These processes are buoyed by a large collection of chaperones and cochaperones, the largest subfamily of which is characterized by the presence of tetratricopeptide repeat (TPR) motifs. TPRs are well characterized protein-protein interaction motifs and have been found on a variety of adapter proteins, either by binding substrate directly or to facilitate the scaffolding of multiprotein complexes. Here, we discuss the major chaperone cycles of the ER and the contribution of TPR-containing proteins to cellular homeostasis within the ER. Recent work in the field has identified the contributions of novel ER TPR-containing proteins to the post-translational modification of secretory proteins. These TPR-containing proteins, the TMTC family, are characterized by long stretches of multiple TPR motifs in a row forming elongated clusters which allow for promiscuous interaction with a wide variety of substrates akin to the ER chaperone SEL1L. However, proteins that contain clusters of 3-4 TPRs have been indicated to mediate specific substrate interaction. To this end, we examine the role of the novel ER resident adapter protein TTC17 in secretory protein trafficking, adding another factor to the complex maturation systems within the ER. There is little to no published work on TTC17, and what little there is often conflicting. Therefore, we fully characterize TTC17 starting from preferential protein isoform expression, to localization, through putative substrate identification. Moreover, we characterize differential expression of TTC17 across disparate tissue and cell lines, indicating possible tissue specific functionality. Leveraging an unbiased quantitative mass spectrometry approach, we rigorously assayed the systemic role TTC17 plays in ER quality control and secretion, confirming its role as a novel ER adapter protein.
dc.description.degreeDoctor of Philosophy (PhD)
dc.description.departmentMolecular and Cellular Biology
dc.identifier.doihttps://doi.org/10.7275/35954610
dc.identifier.orcidhttps://orcid.org/0000-0002-4129-5533
dc.identifier.urihttps://hdl.handle.net/20.500.14394/19350
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=4037&context=dissertations_2&unstamped=1
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.source.statuspublished
dc.subjectendoplasmic reticulum
dc.subjectTTC17
dc.subjecttrafficking
dc.subjectsecretion
dc.subjectglycosylation
dc.subjectCell Biology
dc.subjectMolecular Biology
dc.titlePROTEIN TRAFFICKING IN THE ENDOPLASMIC RETICULUM MEDIATED BY A TPR-CONTAINING ADAPTER PROTEIN
dc.typeopenaccess
dc.typearticle
dc.typedissertation
digcom.contributor.authorisAuthorOfPublication|email:npcanniff@gmail.com|institution:University of Massachusetts Amherst|Canniff, Nathan P
digcom.identifierdissertations_2/2963
digcom.identifier.contextkey35954610
digcom.identifier.submissionpathdissertations_2/2963
dspace.entity.typePublication
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