Localization of Kif1c mRNA to cell protrusions dictates binding partner specificity of the encoded protein
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Updated: Aug 8, 2025

Identification of Kinesin-1 Cargos Using Fluorescence Microscopy
Published on: February 14, 2016
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.
Abstract:
Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In nonneuronal cells, specific mRNAs localize to cell protrusions, and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show that Kif1c mRNA localization does not regulate KIF1C's protein abundance, distribution, or ability to traffic other mRNAs. Conversely, Kif1c mRNA localization to protrusions is required for directed cell migration. We used mass spectrometry to identify binding partners of endogenous KIF1C, which revealed dramatic dysregulation of the number and identity of KIF1C interactors in response to Kif1c mRNA mislocalization. These results therefore uncovered a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein-protein interactions. We anticipate that this mechanism is not limited to Kif1c and is likely to be a general principle that impacts the functions of proteins encoded by protrusion-enriched mRNAs in nonneuronal cells.
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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