A KIF1C-CNBP motor-adaptor complex for trafficking mRNAs to cell protrusions

Konstadinos Moissoglu1, Tianhong Wang1, Alexander N Gasparski1

  • 1Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Cell Reports
|February 21, 2025
PubMed

Insights

This study identifies the RNA-binding protein CNBP as crucial for directing messenger RNA (mRNA) to cell protrusions. CNBP acts as an adaptor, linking mRNA to the kinesin motor KIF1C for transport, aiding cell migration.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • mRNA localization is vital for cellular functions, but mechanisms in complex organisms are not fully understood.
  • Targeting mRNAs to specific cellular locations is often mediated by molecular motors interacting with RNA.
  • Cell migration relies on precise mRNA distribution to cellular protrusions.

Purpose of the Study:

  • To elucidate the molecular mechanism of mRNA transport to mammalian cell protrusions.
  • To identify factors involved in recruiting molecular motors to specific mRNA cargoes.
  • To understand the role of RNA-binding proteins in mRNA trafficking.

Main Methods:

  • RNA immunoprecipitation (RIP) to identify mRNA targets of CNBP.
  • Co-immunoprecipitation (Co-IP) to study protein-protein interactions.
  • Immunofluorescence microscopy to visualize mRNA and protein localization.
  • In vitro binding assays to confirm direct interactions.

Main Results:

  • The RNA-binding protein CNBP directly binds to GA-rich sequences in the 3' UTR of mRNAs destined for cell protrusions.
  • CNBP interacts with the kinesin motor KIF1C.
  • CNBP is essential for recruiting KIF1C to target mRNAs and for their transport along microtubules to the cell periphery.
  • This establishes CNBP as a key adaptor protein in mRNA motor complex formation.

Conclusions:

  • CNBP acts as a crucial adaptor protein, linking specific mRNAs to the KIF1C motor for transport to cell protrusions.
  • This mechanism provides a molecular basis for mRNA localization required for cell migration.
  • The findings reveal a novel motor-adaptor complex essential for mRNA trafficking in higher organisms.

Related Concept Videos

Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
6.7K
Microtubule Associated Motor Proteins01:32

Microtubule Associated Motor Proteins

Eukaryotic cells have different motor proteins for transporting various cargo within the cell. These motor proteins differ based on the filament they associate with, the direction they move within the cell, and the type of cargo they transport. Motor proteins that associate with microtubules are known as microtubule-associated motor proteins. There are two families of microtubule-associated motor proteins —Kinesins and Dyneins. Both these proteins assist in the transport of cellular...
7.6K
Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.7K
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.1K
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K