Recent progress in Alcadein researches

Saori Hata, Megumi Sakuma, Toshiharu Suzuki

Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences and Life Science, Hokkaido University

Alcadeins (Alc) is a type I membrane protein, expressed in neurons, which is linked to amyloid β-protein precursor (APP) through the cytoplasmic adaptor X11L. Both APP and Alc are metabolically stable in the complex, while uncomplexed proteins are subjected to coordinated cleavages resulting in the secretion of short peptides, Aβ or p3 from APP and β-Alc from Alc. Alc and APP function as a cargo receptor of kinesin-1 in neuron. APP connects to kinesin-1 through adaptor JIP1b, while Alc can interact with kinesin-1 directly. Because APP- and Alc-cargos are separately transported in axon with kinesin-1 motor system, excess of Alc cargos or AlcICD (Alc metabolite) blocks the transport of APP cargos, which induces the increased generation of Aβ. Thus, a type of “traffic jam” of APP-cargos may be an affair prior to Aβ generation in the AD pathogenesis.

Address correspondence to Dr. Saori Hata, Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences and Life Science, Hokkaido University (Kita12-Nishi6, Kita-ku, Sapporo 060-0812, Japan)