The ability of the kinesin-2 heterodimer KIF3AC to navigate microtubule networks is provided by the KIF3A motor domain.

Heterodimeric kinesin family member KIF3AC is a mammalian kinesin-2 that is highly expressed in the central nervous system and has been implicated in intracellular transport. KIF3AC is unusual in that the motility characteristics of KIF3C when expressed as a homodimer are exceeding slow, whereas homodimeric KIF3AA, as well as KIF3AC, have much faster ATPase kinetics and single molecule velocities. Heterodimeric KIF3AC and homodimeric KIF3AA and KIF3CC are processive, although the run length of KIF3AC exceeds that of KIF3AA and KIF3CC.

An allosteric propofol-binding site in kinesin disrupts kinesin-mediated processive movement on microtubules.

Microtubule-based molecular motors mediate transport of intracellular cargo to subdomains in neurons. Previous evidence has suggested that the anesthetic propofol decreases the average run-length potential of the major anterograde transporters kinesin-1 and kinesin-2 without altering their velocity. This effect on kinesin has not been observed with other inhibitors, stimulating considerable interest in the underlying mechanism.

Kinesin-2 motors: Kinetics and biophysics.

Kinesin-2s are major transporters of cellular cargoes. This subfamily contains both homodimeric kinesins whose catalytic domains result from the same gene product and heterodimeric kinesins with motor domains derived from two different gene products. In this Minireview, we focus on the progress to define the biochemical and biophysical properties of the kinesin-2 family members.

Homodimeric Kinesin-2 KIF3CC Promotes Microtubule Dynamics.

KIF3C is one subunit of the functional microtubule-based kinesin-2 KIF3AC motor, an anterograde cargo transporter in neurons. However, KIF3C has also been implicated as an injury-specific kinesin that is a key regulator of axonal growth and regeneration by promoting microtubule dynamics for reorganization at the neuronal growth cone. To test its potential role as a modulator of microtubule dynamics in vitro, an engineered homodimeric KIF3CC was incorporated into a dynamic microtubule assay and examined by total internal reflection fluorescence microscopy.

Common general anesthetic propofol impairs kinesin processivity.

Propofol is the most widely used i.v. general anesthetic to induce and maintain anesthesia.

Heterodimerization of Kinesin-2 KIF3AB Modulates Entry into the Processive Run.

Mammalian KIF3AB is an N-terminal processive kinesin-2 that is best known for its roles in intracellular transport. There has been significant interest in KIF3AB to define the key principles that underlie its processivity but also to define the mechanistic basis of its sensitivity to force. In this study, the kinetics for entry into the processive run were quantified.

Kinesin-2 KIF3AC and KIF3AB Can Drive Long-Range Transport along Microtubules.

Mammalian KIF3AC is classified as a heterotrimeric kinesin-2 that is best known for organelle transport in neurons, yet in vitro studies to characterize its single molecule behavior are lacking. The results presented show that a KIF3AC motor that includes the native helix α7 sequence for coiled-coil formation is highly processive with run lengths of ∼1.23 μm and matching those exhibited by conventional kinesin-1.

Myosin 18A coassembles with nonmuscle myosin 2 to form mixed bipolar filaments.

Class-18 myosins are most closely related to conventional class-2 nonmuscle myosins (NM2). Surprisingly, the purified head domains of Drosophila, mouse, and human myosin 18A (M18A) lack actin-activated ATPase activity and the ability to translocate actin filaments, suggesting that the functions of M18A in vivo do not depend on intrinsic motor activity. M18A has the longest coiled coil of any myosin outside of the class-2 myosins, suggesting that it might form bipolar filaments similar to conventional myosins.

Mammalian myosin-18A, a highly divergent myosin.

The Mus musculus myosin-18A gene is expressed as two alternatively spliced isoforms, α and β, with reported roles in Golgi localization, in maintenance of cytoskeleton, and as receptors for immunological surfactant proteins. Both myosin-18A isoforms feature a myosin motor domain, a single predicted IQ motif, and a long coiled-coil reminiscent of myosin-2. The myosin-18Aα isoform, additionally, has an N-terminal PDZ domain.

Drosophila melanogaster myosin-18 represents a highly divergent motor with actin tethering properties.

The gene encoding Drosophila myosin-18 is complex and can potentially yield six alternatively spliced mRNAs. One of the major features of this myosin is an N-terminal PDZ domain that is included in some of the predicted alternatively spliced products. To explore the biochemical properties of this protein, we engineered two minimal motor domain (MMD)-like constructs, one that contains the N-terminal PDZ (myosin-18 M-PDZ) domain and one that does not (myosin-18 M-ΔPDZ).