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Multiple-motor based transport and its regulation by Tau

Vershinin, Michael ; Carter, Brian C ; Razafsky, David S ; King, Stephen J ; Gross, Steven P

Proceedings of the National Academy of Sciences - PNAS, 2007-01, Vol.104 (1), p.87-92 [Periódico revisado por pares]

United States: National Academy of Sciences

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  • Título:
    Multiple-motor based transport and its regulation by Tau
  • Autor: Vershinin, Michael ; Carter, Brian C ; Razafsky, David S ; King, Stephen J ; Gross, Steven P
  • Assuntos: Biological Sciences ; Cells ; Freight ; Freight transport ; Humans ; Kinesin - physiology ; Laser power ; Microtubules ; Microtubules - metabolism ; Motors ; Neurodegenerative Diseases - etiology ; Neurological disorders ; Physiological regulation ; Protein Isoforms ; Protein Transport ; Proteins ; Stall ; tau Proteins - physiology ; Travel ; Trip length
  • É parte de: Proceedings of the National Academy of Sciences - PNAS, 2007-01, Vol.104 (1), p.87-92
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Author contributions: M.V., S.J.K., and S.P.G. designed research; M.V. performed research; M.V., B.C.C., D.S.R., and S.J.K. contributed new reagents/analytic tools; M.V., S.J.K., and S.P.G. analyzed data; and M.V. and S.P.G. wrote the paper.
    Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved November 2, 2006
  • Descrição: Motor-based intracellular transport and its regulation are crucial to the functioning of a cell. Disruption of transport is linked to Alzheimer's and other neurodegenerative diseases. However, many fundamental aspects of transport are poorly understood. An important issue is how cells achieve and regulate efficient long-distance transport. Mounting evidence suggests that many in vivo cargoes are transported along microtubules by more than one motor, but we do not know how multiple motors work together or can be regulated. Here we first show that multiple kinesin motors, working in conjunction, can achieve very long distance transport and apply significantly larger forces without the need of additional factors. We then demonstrate in vitro that the important microtubule-associated protein, tau, regulates the number of engaged kinesin motors per cargo via its local concentration on microtubules. This function of tau provides a previously unappreciated mechanism to regulate transport. By reducing motor reattachment rates, tau affects cargo travel distance, motive force, and cargo dispersal. We also show that different isoforms of tau, at concentrations similar to those in cells, have dramatically different potency. These results provide a well defined mechanism for how altered tau isoform levels could impair transport and thereby lead to neurodegeneration without the need of any other pathway.
  • Editor: United States: National Academy of Sciences
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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