The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Export

@article{citeulike:3337742, abstract = {VAP proteins (human VAPB/ALS8, Drosophila VAP33, and C. elegans VPR-1) are homologous proteins with an amino-terminal major sperm protein (MSP) domain and a transmembrane domain. The MSP domain is named for its similarity to the C. elegans MSP protein, a sperm-derived hormone that binds to the Eph receptor and induces oocyte maturation. A point mutation (P56S) in the MSP domain of human VAPB is associated with Amyotrophic lateral sclerosis (ALS), but the mechanisms underlying the pathogenesis are poorly understood. Here we show that the MSP domains of VAP proteins are cleaved and secreted ligands for Eph receptors. The P58S mutation in VAP33 leads to a failure to secrete the MSP domain as well as ubiquitination, accumulation of inclusions in the endoplasmic reticulum, and an unfolded protein response. We propose that VAP MSP domains are secreted and act as diffusible hormones for Eph receptors. This work provides insight into mechanisms that may impact the pathogenesis of ALS.}, author = {Tsuda, Hiroshi and Han, Sung Min M. and Yang, Youfeng and Tong, Chao and Lin, Yong Qi Q. and Mohan, Kriti and Haueter, Claire and Zoghbi, Anthony and Harati, Yadollah and Kwan, Justin and Miller, Michael A. and Bellen, Hugo J.}, citeulike-article-id = {3337742}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2008.04.039}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18555774}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18555774}, citeulike-linkout-3 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00031951}, day = {13}, doi = {10.1016/j.cell.2008.04.039}, issn = {1097-4172}, journal = {Cell}, keywords = {article, c43f98, c\_elegans, caenorhabditis\_elegans, celegans, efn-2, elegans, f33d1111, m03a11, nematode, vab-1, vpr-1, wormbase}, month = {June}, number = {6}, pages = {963--977}, posted-at = {2008-09-25 18:08:17}, priority = {3}, title = {The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors.}, url = {http://dx.doi.org/10.1016/j.cell.2008.04.039}, volume = {133}, year = {2008} }

TY - JOUR ID - citeulike:3337742 L3 - citeulike-article-id:3337742 N2 - VAP proteins (human VAPB/ALS8, Drosophila VAP33, and C. elegans VPR-1) are homologous proteins with an amino-terminal major sperm protein (MSP) domain and a transmembrane domain. The MSP domain is named for its similarity to the C. elegans MSP protein, a sperm-derived hormone that binds to the Eph receptor and induces oocyte maturation. A point mutation (P56S) in the MSP domain of human VAPB is associated with Amyotrophic lateral sclerosis (ALS), but the mechanisms underlying the pathogenesis are poorly understood. Here we show that the MSP domains of VAP proteins are cleaved and secreted ligands for Eph receptors. The P58S mutation in VAP33 leads to a failure to secrete the MSP domain as well as ubiquitination, accumulation of inclusions in the endoplasmic reticulum, and an unfolded protein response. We propose that VAP MSP domains are secreted and act as diffusible hormones for Eph receptors. This work provides insight into mechanisms that may impact the pathogenesis of ALS. IS - 6 JF - Cell SN - 1097-4172 EP - 977 TI - The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. VL - 133 SP - 963 KW - article KW - c43f98 KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - efn-2 KW - elegans KW - f33d1111 KW - m03a11 KW - nematode KW - vab-1 KW - vpr-1 KW - wormbase AU - Tsuda, Hiroshi AU - Han, Sung Min AU - Yang, Youfeng AU - Tong, Chao AU - Lin, Yong Qi AU - Mohan, Kriti AU - Haueter, Claire AU - Zoghbi, Anthony AU - Harati, Yadollah AU - Kwan, Justin AU - Miller, Michael AU - Bellen, Hugo PY - 2008/06/13/ UR - http://dx.doi.org/10.1016/j.cell.2008.04.039 ER -