title: Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive paralysis due to the selective death of motor neurons of unknown causes. Increasing evidence indicates that Wnt signaling is altered in ALS. In this study, we focused on two non-canonical Wnt signaling components, atypical PKC (aPKC) and a Wnt receptor, Ryk, in a mouse model of ALS, SOD1 (G93A). aPKC mediates Wnt signaling to regulate growth cone guidance, axon differentiation and cell survival. Ryk is a Wnt repulsive receptor that regulates axon guidance and inhibits regeneration after spinal cord injury. aPKC expression was increased in motor neurons of the lumbar spinal cord in SOD1 (G93A) mice at both early and late stages. Interestingly, aPKC was co-localized with SOD1 in motor neuron cell bodies and extracellular aggregates, and aPKC-containing extracellular aggregates increased with disease progression. Biochemical fractionation showed that aPKC protein level was increased in the detergent-insoluble protein fraction in SOD1 (G93A) mice at late stage but decreased in the detergent-soluble fraction at symptomatic stage. These results suggest that aPKC may be sequestered in SOD1 aggregates, impairing its ability to protect motor neurons from death. Ryk expression was also increased in the motor neurons and the white matter in the ventral lumbar spinal cord of mutant SOD1 mice with a peak at early stage. These observations indicate that Wnt/aPKC and Wnt/Ryk signaling are altered in SOD1 (G93A) mice, suggesting that changed Wnt signaling may contribute to neurodegeneration in ALS.
authors.affiliation: University of California, San Diego, Division of Biological Sciences, Section of Neurobiology, 9500 Gilman Drive, La Jolla, California, 92093.
authors.forename: Anna
authors.initials: A
authors.lastname: Tury
authors.forename: Kristine
authors.initials: K
authors.lastname: Tolentino
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C
keywords: ALS; Ryk; SOD1 (G93A); aPKC; neurodegeneration