Organelle-specific control of intracellular transport: Distinctly targeted isoforms of the regulator klar

Yi Guo, Sushrut Jangi, Michael A. Welte

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Microtubule-based transport in cells is powered by a small set of distinct motors, yet timing and destination of transport can be controlled in a cargo-specific manner. The mechanistic basis for this specificity is not understood. To address this question, we analyzed the Drosophila Klarsicht (Klar) protein that regulates distinct microtubule-based transport processes. We find that localization of Klar to its cargoes is crucial for Klar function. Using mutations, we identify functionally important regions of Klar that confer distinct cargo specificity. In ovaries, Klar is present on the nuclear envelope, a localization that requires the C-terminal KASH domain. In early embryos, Klar is attached to lipid droplets, a localization mediated by a novel C-terminal domain encoded by an alternatively spliced exon. In cultured cells, these two domains are sufficient for targeting to the correct intracellular location. Our analysis disentangles Klar's modular organization: we propose that a core region integral to motor regulation is attached to variable domains so that the cell can target regulators with overlapping, yet distinct functions to specific cargoes. Such isoform variation may be a general strategy for adapting a common regulatory mechanism to specifically control motion and positioning of multiple organelles.

Original languageEnglish (US)
Pages (from-to)1406-1416
Number of pages11
JournalMolecular biology of the cell
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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