Identification of soluble WSX-1 not as a dominant-negative but as an alternative functional subunit of a receptor for an anti-Alzheimer's disease rescue factor Humanin.
Humanin (HN) inhibits Alzheimer's disease (AD)-relevant neuronal death and dysfunction, by interacting with a receptor (s) involving ciliary neurotrophic factor receptor alpha (CNTFR), WSX-1, and gp130. It remains unknown whether this complex is the sole HN receptor that mediates HN-induced anti-AD activity. We here report that an alternatively spliced WSX-1 isoform, encoding an extracellular 270-amino-acid region of WSX-1 with cytokine-binding regions (named soluble WSX-1; sWSX-1), is expressed in neuronal cells lacking function of full-length WSX-1 and enables HN to rescue AD-relevant death. This result suggests that CNTFR/soluble WSX-1/gp130 behaves as an alternative functional HN receptor.
Hashimoto
Yuichi
Y
Department of Pharmacology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Kurita
Megumi
M
Matsuoka
Masaaki
M
D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000378:metabolism; D005091:Exons / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor / Q000378:metabolism
D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit; C484747:Il27ra protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C427211:humanin