The ANC-1 (Nesprin-1/2) Organelle-anchoring Protein Functions Through Mitochondria to Polarize Axon Growth in Response to SLT-1

Overview

Journal PLoS Genet

Specialty Genetics

Date 2022 Nov 21

PMID 36409768

Authors

Nathan C Fischer

Vladislav Friedman

Miguel A Martinez-Reyes

Hongyan Hao

Tamjid A Chowdhury

Daniel A Starr

Christopher C Quinn

Affiliations

Soon will be listed here.

Abstract

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.

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