Regulation of the Cytoskeleton by Kinesins

dc.contributor.advisorAlbanesi, Joseph P.en
dc.contributor.committeeMemberCobb, Melanie H.en
dc.contributor.committeeMemberConrad, Nicholasen
dc.contributor.committeeMemberScherer, Philippen
dc.creatorWeil, Lauren Melissaen
dc.date.accessioned2016-01-05T19:38:48Z
dc.date.available2016-01-05T19:38:48Z
dc.date.created2013-12
dc.date.issued2013-11-20
dc.date.submittedDecember 2013
dc.date.updated2016-01-05T19:08:33Z
dc.description.abstractKinesins are motor proteins that associate with microtubules. The position of the motor domain has been linked to kinesin function. While amino-terminal and carboxy-terminal localization of the motor domain is linked to cargo transport, kinesins with the motor domain in the middle (M-kinesins) have a role in microtubule depolymerization. The kinesin-13 family consists of four M-kinesins, KIF2A, KIF2B, KIF2C, and KIF24. These proteins regulate the cytoskeleton through their microtubule depolymerizing activity. All four kinesins have reported functions in mitosis, while little is known about their roles in interphase. KIF2A and KIF2C are upregulated in cancer cells and the increased protein expression influences cell migration and invasiveness. In order to understand how KIF2A and KIF2C influence migration, we analyzed the microtubule and actin cytoskeleton in cells manipulated for kinesin expression. We found that depletion of KIF2A increases the number of focal adhesions and stress fibers and results in defects in cell spreading. KIF2A does not influence the dynamics of focal adhesion assembly or disassembly. In contrast, depletion of KIF2C prevents re-formation of focal adhesions. has little or no effect on the actin cytoskeleton. Here we uncovered a functional divergence in regulation of the cytoskeleton between KIF2A and KIF2C. Furthermore, this is the first time that an M-kinesin, which does not transport cargo, has been shown to influence focal adhesion dynamics.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc933743775
dc.identifier.urihttps://hdl.handle.net/2152.5/2731
dc.language.isoenen
dc.subjectCytoskeletonen
dc.subjectKinesinen
dc.subjectMicrotubulesen
dc.subjectMitosisen
dc.titleRegulation of the Cytoskeleton by Kinesinsen
dc.typeThesisen
dc.type.materialtexten
thesis.date.available2016-01-01
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineCell Regulationen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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