Caldendrin is a Ca2+ binding protein that interacts with multiple effectors, such as the Cav1 L-type Ca2+ channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of caldendrin in Cav1-dependent pathways that impinge upon neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Compared to DRGNs cultured from WT mice, DRGNs of caldendrin knockout (KO) mice exhibited enhanced neurite regeneration and outgrowth. Strong depolarization, which normally represses neurite growth through activation of Cav1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Cav1 channels to growth-inhibitory pathways in DRGNs of females but not males.

Caldendrin is a calmodulin-like Ca2+ binding protein that is expressed primarily in neurons and regulates multiple effectors including Cav1 L-type Ca2+ channels. Here, we tested the hypothesis that caldendrin regulates Cav1-dependent pathways that repress neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Consistent with an inhibitory effect of caldendrin on neurite growth, neurite initiation and growth was enhanced in dissociated DRGNs from caldendrin knockout (KO) mice compared to those from wild type (WT) mice. In an in vitro axotomy assay, caldendrin KO DRGNs grew longer neurites via a mechanism that was more sensitive to inhibitors of transcription as compared to WT DRGNs. Strong depolarization, which normally represses neurite growth through activation of Cav1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Cav1 channels to growth-inhibitory pathways in DRGNs of females but not males. Our findings suggest that caldendrin KO mice represent an ideal model in which to interrogate the transcriptional pathways controlling neurite regeneration and how these pathways may differ in males and females.