Facial motor neuron regeneration induces a unique spatial and temporal pattern of myristoylated alanine-rich C kinase substrate expression

We have previously shown that the myristoylated alanine-rich C kinase subst rate, a primary protein kinase C substrate in brain that binds and cross-li nks filamentous actin, is enriched in neuronal growth cones and is developm entally regulated in brain. Here we examined myristoylated alanine-rich C k inase substrate expression in the facial motor nucleus during axonal regene ration following facial nerve axotomy or facial nerve resection lesions, wh ich impede regeneration, or following motor neuron degeneration induced by the retrograde neurotoxin ricin. For comparative purposes, the protein kina se C substrates myristoylated alanine-rich C kinase substrate-like protein and growth-associated protein-43 were examined in parallel. Myristoylated a lanine-rich C kinase substrate messenger RNA exhibited a robust increase in both neurons and non-neuronal cells in the facial motor nucleus beginning four days after axotomy, peaked at seven days (2.5-fold), and declined back to baseline levels by 40 days. Myristoylated alanine-rich C kinase substra te protein similarly exhibited a twofold elevation in the facial motor nucl eus determined four and 14 days post axotomy. Following nerve resection, my ristoylated alanine-rich C kinase substrate messenger RNA levels increased at seven days and returned to baseline levels by 40 days. Unlike myristoyla ted alanine-rich C kinase substrate messenger RNA, myristoylated alanine-ri ch C kinase substrate-like messenger RNA levels did not increase in the fac ial motor nucleus at any time point following nerve axotomy or resection, w hereas growth-associated protein-43 messenger RNA exhibited a rapid (one da y) and prolonged (40 days) elevation in facial motor nucleus neurons follow ing either nerve axotomy or resection. Ricin-induced degeneration of facial motor neurons elevated myristoylated alanine-rich C kinase substrate and m yristoylated alanine-rich C kinase substrate-like messenger RNAs in both mi croglia (lectin-positive) and astrocytes (glial fibrillary acidic protein-p ositive). Collectively, these data demonstrate that myristoylated alanine-rich C kina se substrate exhibits a unique expression profile in the facial motor nucle us following facial nerve lesions, and it is proposed that myristoylated al anine-rich C kinase substrate may serve to mediate actin-membrane cytoskele tal plasticity in both neurons and glial cells in response to protein kinas eC-mediated signaling during nerve regeneration and degeneration. (C) 2000 IBRO. Published by Elsevier Science Ltd.