Abstract
Mixed polarity microtubule organization is the signature characteristic of vertebrate dendrites. Oppositely oriented microtubules form the basis for selective cargo trafficking in neurons, however the mechanisms that establish and maintain this organization are unclear. Here, we show that APC2, the brain-specific homolog of tumor-suppressor protein adenomatous polyposis coli (APC), promotes dynamics of minus-end-out microtubules in dendrites. We found that APC2 localizes as distinct clusters along microtubule bundles in dendrites and that this localization is driven by LC8-binding and two separate microtubule-interacting domains. Depletion of APC2 reduces the plus end dynamics of minus-end-out oriented microtubules, increases microtubule sliding, and causes defects in dendritic morphology. We propose a model in which APC2 regulates dendrite development by promoting dynamics of minus-end-out microtubules.
Highlights
Mixed polarity microtubule organization is the signature characteristic of vertebrate dendrites
We found that control and adenomatous polyposis coli 2 (APC2) depleted neurons contained similar levels of functional dendritic spine markers Homer and Bassoon
We investigated the role of APC2 in regulation of vertebrate dendrite development
Summary
Mixed polarity microtubule organization is the signature characteristic of vertebrate dendrites. We show that APC2, the brain-specific homolog of tumor-suppressor protein adenomatous polyposis coli (APC), promotes dynamics of minus-end-out microtubules in dendrites. We propose a model in which APC2 regulates dendrite development by promoting dynamics of minus-end-out microtubules. The mechanism to organize and maintain mixed polarity microtubule orientations in vertebrate dendrites is largely unclear. In Drosophila neurons, APC2 is localized to branch points in dendrites and directs microtubule growth in complex with APC, kinesin-2 and EB1 to maintain uniform minus-end-out microtubule polarity specific to Drosophila dendrites[22,23]. We find that during neuronal development, APC2 localizes in dendrites in distinct clusters along microtubules This localization is determined by LC8 (DYNLL2) binding, + TIP interactions and the microtubulebinding domain within the C-terminus tail. We propose a model in which APC2 regulates dendrite development by anchoring along newly polymerized microtubules and establishing potential rescue points, thereby increasing dynamicity of the dendritic microtubule cytoskeleton
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