Growth Signaling in CMT1A

Myelinating Schwann Cells wrap around peripheral axons and allow fast neural transmission. Peripheral myelin protein 22 (PMP22) is a transmembrane glycoprotein strongly expressed by Schwann cells. Alterations in PMP22 expression lead to motor and sensory neuropathies whereas the most frequent form is Charcot-Marie-Tooth disease 1A (CMT1A) due to a duplication of chromosome 17p11.2-12 which leads to PMP22 overexpression. It is known that in the healthy Schwann cell PMP22 is shuttled through the secretory pathway via the endoplasmatic reticulum (ER) and golgi network and is then inserted in the plasma membrane but the proteins role in compact myelin is largely unknown.

Myelinating schwann cell-dorsal root ganglia co-culture (myelin in green, axons in red and nuclei in blue).

Myelinating schwann cell-dorsal root ganglia co-culture (myelin in green, axons in red and nuclei in blue).

Fledrich et al., 2014, showed that one of the major myelination pathways PI3K/AKT/mTOR is downregulated in CMT1A. Using a rat and mouse animal model for CMT1A (Sereda et al., 1996; Huxley et al., 1998) we want to elucidate the function of PMP22 in the Schwann cell signaling. Understanding the molecular function of PMP22 in health and disease is necessary to develop treatment for CMT1A.