Abstract
Proper organization of microtubule networks depends on
microtubule-associated proteins and motors that use
different spatial cues to guide microtubule growth [1–3].
For example, it has been proposed that the uniform
minus-end-out microtubule organization in dendrites of
Drosophila neurons is maintained by steering of polymerizing
microtubules along the stable ones by kinesin-2 motors
bound to growing microtubule plus ends [4]. To explore
the mechanics of kinesin-guided microtubule growth, we reconstituted
this process in vitro. In the presence of microtubule
plus-end tracking EB proteins, a constitutively active
kinesin linked to the EB-interacting motif SxIP effectively
guided polymerizing microtubules along other microtubules
both in cells and in vitro. Experiments combined
with modeling revealed that at angles larger than 90, guidance
efficiency is determined by the force needed for microtubule
bending. At angles smaller than 90, guidance
requires microtubule growth, and guidance efficiency depends
on the ability of kinesins to maintain contact between
the two microtubules despite the geometrical constraints
imposed by microtubule length and growth rate. Our findings
provide a conceptual framework for understanding
microtubule guidance during the generation of different
types of microtubule arrays.
microtubule-associated proteins and motors that use
different spatial cues to guide microtubule growth [1–3].
For example, it has been proposed that the uniform
minus-end-out microtubule organization in dendrites of
Drosophila neurons is maintained by steering of polymerizing
microtubules along the stable ones by kinesin-2 motors
bound to growing microtubule plus ends [4]. To explore
the mechanics of kinesin-guided microtubule growth, we reconstituted
this process in vitro. In the presence of microtubule
plus-end tracking EB proteins, a constitutively active
kinesin linked to the EB-interacting motif SxIP effectively
guided polymerizing microtubules along other microtubules
both in cells and in vitro. Experiments combined
with modeling revealed that at angles larger than 90, guidance
efficiency is determined by the force needed for microtubule
bending. At angles smaller than 90, guidance
requires microtubule growth, and guidance efficiency depends
on the ability of kinesins to maintain contact between
the two microtubules despite the geometrical constraints
imposed by microtubule length and growth rate. Our findings
provide a conceptual framework for understanding
microtubule guidance during the generation of different
types of microtubule arrays.
Original language | English |
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Pages (from-to) | 322-328 |
Journal | Current Biology |
Volume | 24 |
Issue number | 3 |
DOIs | |
Publication status | Published - 3 Feb 2014 |