Modulation of Agrin Function by Alternative Splicing and Ca2+ Binding

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Alternative Splicing of Agrin Alters Its Binding to Heparin, Dystroglycan, and the Putative Agrin Receptor

Agrin is a heparan sulfate proteoglycan that induces aggregation of acetylcholine receptors (AChRs) at the neuromuscular synapse. This aggregating activity is modulated by alternative splicing. Here, we compared binding of agrin isoforms to heparin, alpha-dystroglycan, and cultured myotubes. We find that the alternatively spliced 4 amino acids insert (KSRK) is required for heparin binding. The ...

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Developmental expression and alternative splicing of chick agrin RNA.

Agrin is a synaptic basal lamina protein that has been proposed to mediate motor neuron-induced clustering of acetylcholine receptors during development of the neuro-muscular junction. The chick ciliary ganglion is a parasympathetic ganglion that contains motor neurons that project to striated and smooth muscle targets in the eye. We have examined agrin gene expression in the chick ciliary gang...

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Alternative splicing of agrin regulates its binding to heparin alpha-dystroglycan, and the cell surface.

Agrin is a basal lamina molecule that directs key events in postsynaptic differentiation, most notably the aggregation of acetylcholine receptors (AChRs) on the muscle cell surface. Agrin's AChR clustering activity is regulated by alternative mRNA splicing. Agrin splice forms having inserts at two sites (y and z) in the C-terminal region are highly active, but isoforms lacking these inserts are...

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Alternative RNA splicing that determines agrin activity regulates binding to heparin and alpha-dystroglycan.

Agrin is a component of the extracellular matrix that regulates aspects of neuromuscular junction differentiation. Identification of agrin-binding proteins has lead to the suggestion that alpha-dystroglycan is a muscle cell surface proteoglycan that mediates agrin activity. To further test this hypothesis, we have compared the ability of differentially active agrin isoforms to interact with a m...

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Role of Aberrant Alternative Splicing in Cancer

Alternative splicing can alter genome sequence and as a consequence, many genes change to oncogenes. This event can also affect protein function and diversity. The growing number of study elucidate the pathological influence of impaired alternative splicing events on numerous disease including cancer. Here, we would like to highlight the significant role of alternative splicing in cancer biolog...

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ژورنال

عنوان ژورنال: Structure

سال: 2004

ISSN: 0969-2126

DOI: 10.1016/j.str.2004.02.001