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. 2023 Mar 1;136(5):jcs260735.
doi: 10.1242/jcs.260735. Epub 2023 Mar 3.

Causes, costs and consequences of kinesin motors communicating through the microtubule lattice

Kristen J Verhey  1 , Ryoma Ohi  1
Affiliations

Causes, costs and consequences of kinesin motors communicating through the microtubule lattice

Kristen J Verhey et al. J Cell Sci. .

Abstract

Microtubules are critical for a variety of important functions in eukaryotic cells. During intracellular trafficking, molecular motor proteins of the kinesin superfamily drive the transport of cellular cargoes by stepping processively along the microtubule surface. Traditionally, the microtubule has been viewed as simply a track for kinesin motility. New work is challenging this classic view by showing that kinesin-1 and kinesin-4 proteins can induce conformational changes in tubulin subunits while they are stepping. These conformational changes appear to propagate along the microtubule such that the kinesins can work allosterically through the lattice to influence other proteins on the same track. Thus, the microtubule is a plastic medium through which motors and other microtubule-associated proteins (MAPs) can communicate. Furthermore, stepping kinesin-1 can damage the microtubule lattice. Damage can be repaired by the incorporation of new tubulin subunits, but too much damage leads to microtubule breakage and disassembly. Thus, the addition and loss of tubulin subunits are not restricted to the ends of the microtubule filament but rather, the lattice itself undergoes continuous repair and remodeling. This work leads to a new understanding of how kinesin motors and their microtubule tracks engage in allosteric interactions that are critical for normal cell physiology.

Keywords: GTP island; Kinesin; Microtubule; Microtubule lattice; Microtubule repair; Tubulin; Tubulin code.

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Conflict of interest statement

Competing interests The authors declare no competing or financial interests.

Figures

Fig. 1.
Fig. 1.
Microtubule dynamics. Tubulin subunits (dimers of α- and β-tubulin) self-assemble in a head-to-tail fashion to form a cylindrical microtubule. Tubulin subunits with GTP bound to β-tubulin (GTP-tubulin, dark blue) can undergo polymerization (microtubule growth), whereas tubulin subunits with GDP bound to β-tubulin (GDP-tubulin, light blue) fall off the polymer (microtubule shrinkage). GTP hydrolysis drives a structural change in tubulin from an expanded conformation (thick outline) to a compacted conformation (thin outline). Tubulin subunits within the GDP-lattice can be altered by posttranslational modifications (PTMs, magenta circles) or by adopting the expanded conformation (thick outline).
Fig. 2.
Fig. 2.
Kinesin structure and motility. (A) General schematic of a dimeric kinesin motor protein showing the motor, stalk and tail domains. (B) Processive motility of a truncated (constitutively active) kinesin along the microtubule surface. Alternating ATP hydrolysis by the two motor domains enables stepping (movement from one tubulin subunit to the next) along a protofilament of a microtubule. In the absence of nucleotide or in the presence of the non-hydrolyzable analog AMPPNP, kinesins bind statically to the microtubule surface. T, ATP; D, ADP; N, AMPPNP; −, no nucleotide.
Fig. 3.
Fig. 3.
Kinesin-1 can write and read the tubulin state in the microtubule lattice. (A) Kinesin-1 reads the tubulin state and binds preferentially to microtubules containing tubulins marked by specific PTMs (magenta circles) or tubulins in the GTP-like/expanded state (thick outline). (B) Static kinesin-1 binding writes an expanded state to a GDP-lattice, enabling through-the-lattice allostery (yellow arrows) with other motors. (C) Walking kinesin-1 writes a GTP-tubulin (expanded) state by creating damage sites in the lattice that can be repaired by soluble GTP-tubulin.
Fig. 4.
Fig. 4.
Kinesin-1 and kinesin-4 motors communicate allosterically through the microtubule lattice. (A) Individual kinesin-4 motors do not accumulate at microtubule ends because their run length is too short (small purple arrow). (B,C) While walking, (B) kinesin-4 and (C) kinesin-1 motors write changes to the microtubule that work allosterically through the lattice (yellow arrows) to influence other kinesin-4 motors. The increase in binding and motility of kinesin-4 (large purple arrow) enables its accumulation at microtubule ends.
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