HSP90 is a chaperone for DLK and is required for axon injury signaling

Abstract

Significance Defining mechanisms of axon injury signaling is critical to understand axon regeneration. This knowledge can be used to develop strategies of axonal repair. Identification of such injury signals has been limited by traditional in vivo assays of proregenerative injury signaling. Here, we describe an in vitro screening platform that specifically identifies proregenerative axon injury signals in mouse neurons. We show that HSP90 is required for injury signaling and detail a mechanism by which HSP90 chaperones the essential proregenerative kinase, dual leucine zipper kinase (DLK). Thus, this work also describes HSP90 as a previously unidentified regulator of DLK, a critical neuronal stress sensor that drives axon regeneration, degeneration, and neurological disease.