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Title:Studies of Huntington's disease associated motor domain phosphorylation of kinesin-1
Author(s):DeBerg, Hannah
Director of Research:Selvin, Paul R.
Doctoral Committee Chair(s):Chemla, Yann R.
Doctoral Committee Member(s):Selvin, Paul R.; Aksimentiev, Aleksei; Kwiat, Paul G.
Department / Program:Physics
Discipline:Physics
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Kinesin
Microtubule Motors
Huntington's Disease
Motor Protein
Abstract:In neurons, microtubule motor driven transport is crucial for communication between processes and the cell body. Disruptions in transport are associated with a variety of neurodegenerative diseases. Recent studies implicate phosphorylation of serine 175, a conserved residue found in all three isoforms of kinesin-1 in impaired axonal transport associated with Huntington’s disease. Phosphorylation adds both negative charge and bulk to a protein. The mechanism by which S175 modification is related to impaired transport is not very well understood. It is not known whether phosphorylation of kinesin alone is sufficient to cause impaired cargo transport. To investigate the isolated effect of residue 175 on kinesin transport, we used optical trapping and single-molecule fluorescence imaging to study purified kinesin. We found no significant difference in the processivity or ATPase activity of a phosphomimetic S175D construct or the non-phosphorylatable S175A construct. However, we did find that addition of a negative charge at S175 through phosphorylation or mutation led to a decreased stall force. Furthermore, polystyrene bead cargos coated with dynein and kinesin traveled preferentially in the minus direction when residue 175 of kinesin was negatively charged. These results show that modification of serine 175 alone is sufficient to alter the behavior of kinesin.
Issue Date:2013-05-24
URI:http://hdl.handle.net/2142/44331
Rights Information:Copyright 2013 Hannah DeBerg
Date Available in IDEALS:2013-05-24
Date Deposited:2013-05


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