Light chain-dependent regulation of kinesin's interaction with microtubules

Kristen J. Verhey, Donna L. Lizotte, Tatiana Abramson, Linda Barenboim, Bruce Schnapp, Tom A. Rapoport

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

We have investigated the mechanism by which conventional kinesin is prevented from binding to microtubules (MTs) when not transporting cargo. Kinesin heavy chain (HC) was expressed in COS cells either alone or with kinesin light chain (LC). Immunofluorescence microscopy and MT cosedimentation experiments demonstrate that the binding of HC to MTs is inhibited by coexpression of LC. Association between the chains involves the LC NH2-terminal domain, including the heptad repeats, and requires a region of HC that includes the conserved region of the stalk domain and the NH2 terminus of the tail domain. Inhibition of MT binding requires in addition the COOH-terminal 64 amino acids of HC. Interaction between the tail and the motor domains of HC is supported by sedimentation experiments that indicate that kinesin is in a folded conformation. A pH shift from 7.2 to 6.8 releases inhibition of kinesin without changing its sedimentation behavior. Endogenous kinesin in COS cells also shows pH-sensitive inhibition of MT binding. Taken together, our results provide evidence that a function of LC is to keep kinesin in an inactive ground state by inducing an interaction between the tail and motor domains of HC; activation for cargo transport may be triggered by a small conformational change that releases the inhibition of the motor domain for MT binding.

Original languageEnglish (US)
Pages (from-to)1053-1066
Number of pages14
JournalJournal of Cell Biology
Volume143
Issue number4
DOIs
StatePublished - Nov 16 1998
Externally publishedYes

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Kinesin
Microtubules
Light
COS Cells
Fluorescence Microscopy
Amino Acids

Keywords

  • Kinesin
  • Microtubules
  • Molecular motors

ASJC Scopus subject areas

  • Cell Biology

Cite this

Verhey, K. J., Lizotte, D. L., Abramson, T., Barenboim, L., Schnapp, B., & Rapoport, T. A. (1998). Light chain-dependent regulation of kinesin's interaction with microtubules. Journal of Cell Biology, 143(4), 1053-1066. https://doi.org/10.1083/jcb.143.4.1053

Light chain-dependent regulation of kinesin's interaction with microtubules. / Verhey, Kristen J.; Lizotte, Donna L.; Abramson, Tatiana; Barenboim, Linda; Schnapp, Bruce; Rapoport, Tom A.

In: Journal of Cell Biology, Vol. 143, No. 4, 16.11.1998, p. 1053-1066.

Research output: Contribution to journalArticle

Verhey, KJ, Lizotte, DL, Abramson, T, Barenboim, L, Schnapp, B & Rapoport, TA 1998, 'Light chain-dependent regulation of kinesin's interaction with microtubules', Journal of Cell Biology, vol. 143, no. 4, pp. 1053-1066. https://doi.org/10.1083/jcb.143.4.1053
Verhey, Kristen J. ; Lizotte, Donna L. ; Abramson, Tatiana ; Barenboim, Linda ; Schnapp, Bruce ; Rapoport, Tom A. / Light chain-dependent regulation of kinesin's interaction with microtubules. In: Journal of Cell Biology. 1998 ; Vol. 143, No. 4. pp. 1053-1066.
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