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Published online
doi:10.1083/jcb.1786iti5
The Journal of Cell Biology, Vol. 178, No. 6, 890-
The Rockefeller University Press, 0021-9525 $30.00
© LeBrasseur
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Kinesin-5 reins in axon branching



Figure 1
Axons branch wildly without kinesin-5 (bottom).

The motor that puts a brake on spindle microtubule sliding also decelerates axon branching, report Myers and Baas.

The spindle brake is kinesin-5. Unlike most microtubule-based motors, the "cargo" of kinesin-5 is more microtubules. In dividing cells, this motor bundles oppositely oriented spindle microtubules and seems to help drive them apart. Recent work shows that kinesin-5 can also prevent them from sliding past each other too quickly, thus preventing premature pole separation.

Kinesin-5 also has a strong presence in developing neurons, which are done dividing and would thus seem not to need a spindle brake. Because its inhibition creates longer axons, Myers and Baas imagined that kinesin-5 normally transports short microtubule building blocks from the axon back to the cell body. In its absence, they figured, more blocks would be available for axon growth.

Instead, the authors found that short microtubules were transported twice as frequently without kinesin-5, both into and out of axons. The increase in transport and axon length was accompanied by an increase in axon branching. Normally, axons send out many new branches, most of which collapse back into the growth cone. But these retraction events were rare without kinesin-5.

Retraction is a result of myosin-2's pulling force on the actin cytoskeleton. Dynein can counteract this force by hooking actin to long structural support microtubules. The authors now hypothesize that kinesin-5 opposes dynein, thus allowing retraction to occur. They suggest that it might do so by physically replacing dynein or by bundling microtubules, thereby increasing dynein's load.

Drugs that block kinesin-5 activity are already in use as cancer therapies, thanks to their antimitotic effects. If kinesin-5 is also expressed in adult axons, the drugs might find secondary uses in prodding the regeneration of damaged axons. Formula

Reference:

Myers, K.A., and P.W. Baas. 2007. J. Cell Biol. 178:1081–1091.[Abstract/Free Full Text]



Nicole LeBrasseur

lebrasn{at}rockefeller.edu


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Related Article

Kinesin-5 regulates the growth of the axon by acting as a brake on its microtubule array
Kenneth A. Myers and Peter W. Baas
J. Cell Biol. 2007 178: 1081-1091. [Abstract] [Full Text] [PDF]




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