التفاصيل البيبلوغرافية
| العنوان: |
Cellular localization of a variant RAPGEF5 protein associated with idiopathic epilepsy risk in the Belgian shepherd. |
| المؤلفون: |
Cayabyab, Dawn D., Belanger, Janelle M., Xu, Claudia, Maga, Elizabeth A., Oberbauer, Anita M. |
| المصدر: |
Canine Medicine & Genetics; 9/29/2024, Vol. 11 Issue 1, p1-6, 6p |
| مصطلحات موضوعية: |
GREEN fluorescent protein, WNT signal transduction, CELLULAR signal transduction, NEUROLOGICAL disorders, EMBRYOLOGY |
| مستخلص: |
The Wnt signaling pathway is critical for normal embryonic development. Disruptions in the Wnt signaling pathway have been linked to neurological disorders. The RAPGEF5 protein is a partner in Wnt signaling and a RAPGEF5 3-bp insertion is associated with increased risk for idiopathic epilepsy in the Belgian shepherd dog. The 3-bp insertion risk variant introduces an alanine residue predicted to disrupt the protein. Wildtype and the risk variant RAPGEF5 cDNAs were cloned into green fluorescent protein (GFP) expression vectors and transfected into canine kidney cells. The cellular localization of each GFP-labeled RAPGEF5 protein was assessed. Variant RAPGEF5 protein was altered in its localization from that of the wildtype protein and rather than localized to the nucleus and cytoplasm as seen for the wildtype, it was predominantly found in the cytoplasm. Belgian shepherds with the risk variant for RAPGEF5 may have altered Wnt signaling due to modified intracellular localization which in turn could thereby contribute to the expression of idiopathic epilepsy. Plain English Summary: A small insertion in the RAPGEF5 gene is shown to be associated with an increased risk for idiopathic epilepsy in Belgian Shepherds. The insertion introduces an additional amino acid that is predicted to disrupt the RAPGEF5 protein. This protein is involved in the Wnt signaling pathway which is critical for normal embryonic development and disturbances in the Wnt pathway have been linked to neurological disorders. To determine the impact of the insertion on RAPGEF5 function, coding DNA sequences for both the normal and risk variant RAPGEF5 were cloned into a fluorescent expression vector and transfected into cultured canine kidney cells. The cellular location of the labeled RAPGEF5 proteins was then visually assessed. In contrast to the localization of the normal protein to the nucleus, the risk variant protein was located predominantly in the cytoplasm. With this altered location within the cell, the risk variant protein may alter the Wnt signaling pathway and contribute to the idiopathic epilepsy observed in Belgian Shepherds. [ABSTRACT FROM AUTHOR] |
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