RESUMEN

Schwann cell-derived peripheral myelin protein-22 (PMP-22) when mutated or overexpressed causes heritable neuropathies with a previously unexplained "gain-of-function" endoplasmic reticulum (ER) retention phenotype. In wild-type sciatic nerves, PMP-22 associates in a specific, transient (t(1/2 ) approximately equal to 11 min), and oligosaccharide processing-dependent manner with the lectin chaperone calnexin (CNX), but not calreticulin nor BiP. In Trembler-J (Tr-J) sciatic nerves, prolonged association of mutant PMP-22 with CNX is found (t(1/2) > 60 min). In 293A cells overexpressing PMP-22(Tr-J), CNX and PMP-22 colocalize in large intracellular structures identified at the electron microscopy level as myelin-like figures with CNX localization in the structures dependent on PMP-22 glucosylation. Similar intracellular myelin-like figures were also present in Schwann cells of sciatic nerves from homozygous Trembler-J mice with no detectable activation of the stress response pathway as deduced from BiP and CHOP expression. Sequestration of CNX in intracellular myelin-like figures may be relevant to the autosomal dominant Charcot-Marie-Tooth-related neuropathies.

Asunto(s)

Proteínas de Unión al Calcio/metabolismo , Proteínas de la Mielina/metabolismo , Enfermedades del Sistema Nervioso/fisiopatología , Nervio Ciático/fisiología , Animales , Secuencia de Bases , Células COS , Calnexina , Línea Celular , Chlorocebus aethiops , Cartilla de ADN , Células HeLa , Humanos , Proteínas de la Membrana/metabolismo , Ratones , Proteínas de la Mielina/genética , Enfermedades del Sistema Nervioso/genética , Reacción en Cadena de la Polimerasa , Ratas , Proteínas Recombinantes de Fusión/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

Asunto(s)

Membrana Celular , Computadores , Modelos Biológicos , Colesterol , Matemática , Proteínas