Kinesin superfamily proteins (KIFs) are molecular motors that drive directional, microtubule-dependent intracellular transport of membrane-bound organelles and other macromolecules (e.g. proteins, nucleic acids). The intracellular transport functions of KIFs are fundamentally important for a variety of cellular functions, including mitotic and meiotic division, motility/migration, hormone and neurotransmitter release, and differentiation. Disruptions to KIF-mediated intracellular transport have been linked with a variety of pathologies, ranging from tumorigenesis to defects in higher order brain function such as learning and memory. Kinesin superfamily protein 3A (KIF3A) is a central component of the kinesin-2 protein complex. KIF3A and its paralog KIF3B bind to form a heterodimeric motor protein with ATP-dependent, plus-end-directed microtubule sliding activity. The tail domain of this heterodimer binds to kinesin-associated protein 3 (KAP3), which facilitates binding of the KIF3A/3B motor protein to its cargo. Recent studies in a variety of model organisms have demonstrated a critical role for kinesin-family proteins, including KIF3A, in the formation and function of cilia. Notably, KIF3A was shown to mediate cilia-dependent protein-protein interactions that function to transduce canonical Hedgehog signaling. |