Localization of Kif1c mRNA to cell protrusions dictates binding partner specificity of the encoded protein

Megan L Norris1, Joshua T Mendell1,2,3,4

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; joshua.mendell@utsouthwestern.edu megan.norris@utsouthwestern.edu.

Genes & Development
|March 1, 2023
PubMed

Insights

Messenger RNA (mRNA) localization to cell protrusions is crucial for directed cell migration. Mislocalizing KIF1C mRNA alters protein interactions, revealing a new mechanism for mRNA

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Subcellular mRNA localization regulates protein function, particularly in cell migration.
  • The precise mechanisms linking mRNA localization to protein function in cell protrusions are not well understood.

Purpose of the Study:

  • To investigate the functional consequences of KIF1C mRNA localization in nonneuronal cells.
  • To elucidate the role of KIF1C mRNA localization in cell migration and protein-protein interactions.

Main Methods:

  • Studied the effects of KIF1C mRNA mislocalization on KIF1C protein properties.
  • Utilized mass spectrometry to identify KIF1C binding partners.
  • Assessed the requirement of KIF1C mRNA localization for directed cell migration.

Main Results:

  • KIF1C mRNA localization to protrusions is essential for directed cell migration.
  • Mislocalization of KIF1C mRNA does not affect KIF1C protein abundance, distribution, or its mRNA trafficking capabilities.
  • KIF1C mRNA mislocalization leads to significant changes in the number and identity of KIF1C protein interactors.

Conclusions:

  • mRNA localization to cell protrusions directly influences protein-protein interaction specificity.
  • This mechanism provides a novel link between mRNA localization and protein function in cell migration.
  • The findings suggest a general principle for how protrusion-enriched mRNAs regulate protein function in nonneuronal cells.

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