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Cram, Jennifer Patritti

https://orcid.org/0000-0001-5971-0849

Mayo Clinic

Cincinnati Children's Hospital Medical Center

Citations 2

Author response: P2RY14 cAMP signaling regulates Schwann cell precursor self-renewal, proliferation, and nerve tumor initiation in a mouse model of neurofibromatosis
Cram, Jennifer Patritti , Coover, Robert A. , Rizvi, Tilat A. , Chaney, Katherine E. , Ravindran, Ramya , Spinner, Robert J. , Wu, Jianqiang , Cancelas, José A. , Ratner, Nancy

No container title available | March 28, 2022 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.7554/elife.73511.sa2 Get It

P2RY14 cAMP signaling regulates Schwann cell precursor self-renewal, proliferation, and nerve tumor initiation in a mouse model of neurofibromatosis
Cram, Jennifer Patritti , Wu, Jianqiang , Coover, Robert A, Rizvi, Tilat A, Chaney, Katherine E, Ravindran, Ramya, Cancelas, Jose A, Spinner, Robert J, Ratner, Nancy , Ravindran, Ramya , Patritti Cram, Jennifer , Wu, Jianqiang , Coover, Robert A, Rizvi, Tilat A, Chaney, Katherine E, Ravindran, Ramya, Cancelas, Jose A, Spinner, Robert J, Ratner, Nancy

eLife | March 21, 2022 | Volume: 11 | Issue: No issue available | Pages: No page available

10.7554/elife.73511 Get It

Neurofibromatosis type 1 (NF1) is characterized by nerve tumors called neurofibromas, in which Schwann cells (SCs) show deregulated RAS signaling. NF1 is also implicated in regulation of cAMP. We identified the G-protein-coupled receptor (GPCR) P2ry14 in human neurofibromas, neurofibroma-derived SC precursors (SCPs), mature SCs, and mouse SCPs. Mouse Nf1-/- SCP self-renewal was reduced by genetic or pharmacological inhibition of P2ry14. In a mouse model of NF1, genetic deletion of P2ry14 rescued low cAMP signaling, increased mouse survival, delayed neurofibroma initiation, and improved SC Remak bundles. P2ry14 signals via G i to increase intracellular cAMP, implicating P2ry14 as a key upstream regulator of cAMP. We found that elevation of cAMP by either blocking the degradation of cAMP or by using a P2ry14 inhibitor diminished NF1 -/- SCP self-renewal in vitro and neurofibroma SC proliferation in in vivo. These studies identify P2ry14 as a critical regulator of SCP self-renewal, SC proliferation, and neurofibroma initiation.