title: Adducin at the Neuromuscular Junction in Amyotrophic Lateral Sclerosis: Hanging on for Dear Life.
abstract: The neurological dysfunction in amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules (CAMs) linking the pre- and post-synaptic components of the neuromuscular junction (NMJ) are involved. To search for candidate proteins implicated in this degenerative process, researchers have studied the Drosophila larval NMJ and find that the cytoskeleton-associated protein, adducin, is ideally placed to regulate synaptic contacts. By controlling the levels of synaptic proteins, adducin can de-stabilize synaptic contacts. Interestingly, elevated levels of phosphorylated adducin have been reported in ALS patients and in a mouse model of the disease. Adducin is regulated by phosphorylation through protein kinase C (PKC), some isoforms of which exhibit Ca(2+)-dependence, raising the possibility that changes in intracellular Ca(2+) might alter PKC activation and secondarily influence adducin phosphorylation. Furthermore, adducin has interactions with the alpha subunit of the Na(+)/K(+)-ATPase. Thus, the phosphorylation of adducin may secondarily influence synaptic stability at the NMJ and so influence pre- and post-synaptic integrity at the NMJ in ALS.
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser University Burnaby, BC, Canada.
authors: Charles
authors: C
authors: Krieger
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser UniversityBurnaby, BC, Canada; Department of Molecular Biology and Biochemistry, Simon Fraser UniversityBurnaby, BC, Canada.
authors: Simon Ji Hau
authors: SJ
authors: Wang
authors: Department of Biomedical Physiology and Kinesiology, Simon Fraser UniversityBurnaby, BC, Canada; Department of Molecular Biology and Biochemistry, Simon Fraser UniversityBurnaby, BC, Canada.
authors: Soo Hyun
authors: SH
authors: Yoo
authors: Department of Molecular Biology and Biochemistry, Simon Fraser University Burnaby, BC, Canada.
authors: Nicholas
authors: N
authors: Harden
keywords: Discs large; Hu-li tai shao; adducin; amyotrophic lateral sclerosis; neural cell adhesion molecule; neuromuscular junction