Reference Report

Reference
Citation	Tsuda, H., Han, S.M., Yang, Y., Tong, C., Lin, Y.Q., Mohan, K., Haueter, C., Zoghbi, A., Harati, Y., Kwan, J., Miller, M.A., Bellen, H.J. (2008). The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell 133(6): 963--977. (Export to RIS)
FlyBase ID	FBrf0205211
Publication Type	Research paper
PubMed ID	18555774
PubMed 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.
DOI	10.1016/j.cell.2008.04.039
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Cell
Title	Cell
Publication Year	1974-
ISBN/ISSN	0092-8674
Data from Reference
Alleles (12)
	Eph^unspecified Hsap\VAPB^Scer\UAS.cCa Scer\GAL4^C5 Scer\GAL4^C164 Scer\GAL4^da.G32 Scer\GAL4^dpp.PS Scer\GAL4^elav-C155 Vap-33-1^{P58S.Scer\UAS} Vap-33-1^Scer\UAS.cPa Vap-33-1^{Scer\UAS.T:Zzzz\FLAG,T:Ivir\HA1} Vap-33-1^Δ20 Vap-33-1^Δ448
Constructs (6)
	P{dpp-GAL4.PS} P{GAL4-da.G32} P{UAS-DVAP-33A.P58S} P{UAS-FLAG.Vap-33-1.HA} P{UAS-Hsap\VAPB.C} P{UAS-Vap-33-1.P}
Genes (10)
	boca Eph Ephrin Hsap\VAPB Hsc70-3 Scer\GAL4 T:Ivir\HA1 T:Zzzz\FLAG Vap-33-1 α-Spec
Insertions (3)
	P{GawB}C5^C5 P{GawB}C164 P{GawB}elav^C155
Natural transposons (1)
	P-element