کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2198864 1099409 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology
چکیده انگلیسی

Most epilepsy genes encode ion channels, but the LGI1 gene responsible for autosomal dominant partial epilepsy with auditory features produces a secreted protein. LGI1 is suggested to regulate PSD-95 via ADAM22. However, no unbiased screen of LGI1 action has been conducted. Here, we searched for brain genes supporting high affinity LGI-1 binding. ADAM23 was the only LGI1 interactor identified. The related proteins, ADAM22 and ADAM11, but not ADAM12, bind LGI1. Neither ADAM23 nor ADAM11, nor some forms of ADAM22, contain PDZ-interacting sequences, suggesting PSD-95-independent mechanisms in ADPEAF. Because ADAMs modulate integrins, we examined LGI1 effect on neurite outgrowth. LGI1 increases outgrowth from wild-type but not ADAM23−/− neurons. Furthermore, CA1 pyramidal neurons of ADAM23−/− hippocampi have reduced dendritic arborization. ADAM23−/− mice exhibit spontaneous seizures, while ADAM23+/− mice have decreased seizure thresholds. Thus, LGI1 binding to ADAM23 is necessary to correctly pattern neuronal morphology and altered anatomical patterning contributes to ADPEAF.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 42, Issue 4, November 2009, Pages 448–457
نویسندگان
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