| First Author | La Montanara P | Year | 2020 |
| Journal | Sci Transl Med | Volume | 12 |
| Issue | 551 | PubMed ID | 32641489 |
| Mgi Jnum | J:292623 | Mgi Id | MGI:6448545 |
| Doi | 10.1126/scitranslmed.aax4846 | Citation | La Montanara P, et al. (2020) Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models. Sci Transl Med 12(551) |
| abstractText | Cyclin-dependent-like kinase 5 (CDKL5) gene mutations lead to an X-linked disorder that is characterized by infantile epileptic encephalopathy, developmental delay, and hypotonia. However, we found that a substantial percentage of these patients also report a previously unrecognized anamnestic deficiency in pain perception. Consistent with a role in nociception, we found that CDKL5 is expressed selectively in nociceptive dorsal root ganglia (DRG) neurons in mice and in induced pluripotent stem cell (iPS)-derived human nociceptors. CDKL5-deficient mice display defective epidermal innervation, and conditional deletion of CDKL5 in DRG sensory neurons impairs nociception, phenocopying CDKL5 deficiency disorder in patients. Mechanistically, CDKL5 interacts with calcium/calmodulin-dependent protein kinase II alpha (CaMKIIalpha) to control outgrowth and transient receptor potential cation channel subfamily V member 1 (TRPV1)-dependent signaling, which are disrupted in both CDKL5 mutant murine DRG and human iPS-derived nociceptors. Together, these findings unveil a previously unrecognized role for CDKL5 in nociception, proposing an original regulatory mechanism for pain perception with implications for future therapeutics in CDKL5 deficiency disorder. |
