Spectraplakin is required for dendritic microtubule organization via a tip-based mechanism

The differential microtubule organization in axons and dendrites underlies neuronal polarity and developmental processes like neurite pruning. How neurons achieve their specific microtubule organization during development is an area of active research, and it has been especially hard to explain how dendritic microtubules are oriented with their plus ends towards the soma. Transient microtubule nucleation from tips of early growing dendrites has been detected in some systems and would explain how orientation is set up. In a survey for cytoskeletal regulators involved in dendrite pruning and microtubule organization in Drosophila, we found the spectraplakin Short stop (Shot), an actin/microtubule crosslinker. Loss of Shot causes microtubule orientation defects already during early dendrite development, when Shot is transiently recruited to tips of growing dendrites via its actin binding domain. Genetic and functional evidence suggest that Shots primary function in this process is to locally stabilize microtubules. We also provide evidence for a developmentally transient microtubule nucleation mechanism. Our data highlight the importance of transient and localized microtubule regulation for dendritic microtubule organization.