kinesin1

Kinesin-1, also known as conventional kinesin, is a dimeric, microtubule-based motor protein that moves cargo toward the plus ends of microtubules. It is a member of the kinesin superfamily and is composed of two kinesin-1 heavy chains, typically KIF5A, KIF5B, and KIF5C in mammals, and two light chains that regulate cargo binding. The heavy chains contain an N-terminal motor domain responsible for ATP hydrolysis and microtubule interaction, a coiled-coil stalk that facilitates dimerization, and a C-terminal tail that links to light chains and cargo adaptors.

Kinesin-1 converts chemical energy from ATP hydrolysis into mechanical work, walking processively along microtubules in a hand-over-hand mechanism with ~8-nanometer steps. Dimerization of the two motor domains enables sustained movement, which is tightly regulated by the motor’s autoinhibitory state: in the absence of cargo, intramolecular interactions suppress motor activity, and activation occurs upon cargo binding through adaptor proteins and, in some cases, phosphorylation.

In cells, kinesin-1 transports a wide range of cargo, including membrane-bound vesicles, endosomes, lysosomes, mitochondria, and various organelles, over long distances along axons and dendrites. It plays a critical role in neuronal development and maintenance by enabling fast, targeted transport required for synaptic function and organelle distribution. The activity and specificity of kinesin-1 are modulated by cargo adaptors and regulatory signals, ensuring proper intracellular logistics.

Mutations in kinesin-1 family genes, particularly KIF5A, have been linked to neurological disorders such as hereditary spastic paraplegia (SPG10) and related neuropathies, highlighting the importance of regulated kinesin-1 function for neural health.