CLN5 deficiency results in alterations in the activation of autophagy

dc.contributor.authorBudden, Theodore
dc.date.accessioned2015-10-12T18:23:09Z
dc.date.available2015-10-12T18:23:09Z
dc.date.graduationmonthAugust
dc.date.issued2014-08-01
dc.date.published2014
dc.description.abstractCLN5 is one of several proteins that when mutated result in the lysosomal storage disorder (LSD) Neuronal Ceroid Lipofuscinosis (NCL). CLN5 is a soluble lysosomal protein that has no known function at this time. Previously we showed that eight asparagine residues in CLN5 are N-glycosylated, and that this modification is important for the protein’s transport and function. Now, we have identified a link between the activation of autophagy and CLN5 deficiency. The autophagy-lysosomal protein degradation system is one of the major pathways the cell uses to degrade intracellular material and recycle cellular building blocks. It was recently shown that other CLN proteins affect the relative level of autophagy, indicating a potential link between the autophagy pathway and the NCLs. By knocking down endogenous CLN5 in HeLa we showed that, upon stress induction, cells responded with higher levels of autophagy activation. Consistent with these knockdown experiments, there is a higher level of the autophagy marker protein, LC3-II, in CLN5 patient cells that are naturally deficient for the CLN5 protein. Pharmaceutical induction of autophagy through different means also showed higher LC3-II levels compared to control, though patterns differed in the type of autophagy induced. In summary, we discovered that the autophagy pathway is altered in CLN5 deficient cells, indicating a potential role for CLN5 in autophagy. Further analyses of the autophagy pathway will shed light on where CLN5 is acting and the mechanism by which defective CLN5 causes NCL.
dc.description.advisorStella Y. Lee
dc.description.degreeMaster of Science
dc.description.departmentDepartment of Biology
dc.description.levelMasters
dc.identifier.urihttp://hdl.handle.net/2097/20473
dc.language.isoen_US
dc.publisherKansas State University
dc.rights© the author. This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectLysosomal storage disorder
dc.subjectAutophagy
dc.subjectNeuronal ceroid lipofuscinoses
dc.subjectCLN5
dc.subject.umiBiology (0306)
dc.titleCLN5 deficiency results in alterations in the activation of autophagy
dc.typeThesis

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