A family of giant KASH proteins, including C. elegans ANC-1 and mammalian Nesprin-1 and -2, are involved in organelle anchoring and are associated with multiple neurodevelopmental disorders including autism, bipolar disorder, and schizophrenia. However, little is known about how these proteins function in neurons. Moreover, the role of organelle anchoring in axon development is poorly understood. Here, we report that ANC-1 functions with the SLT-1 extracellular guidance cue to polarize ALM axon growth. This role for ANC-1 is specific to its longer ANC-1A and ANC-1C isoforms, suggesting that it is mechanistically distinct from previously described roles for ANC-1. We find that ANC-1 is required for the localization of a cluster of mitochondria to the base of the proximal axon. Furthermore, genetic and pharmacological studies indicate that ANC-1 functions with mitochondria to promote polarization of ALM axon growth. These observations reveal a mechanism whereby ANC-1 functions through mitochondria to polarize axon growth in response to SLT-1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.