RT Dissertation/Thesis
T1 Isolation of VGF derived neuropeptide receptor
A1 Akhter, Shamim
A2 Universidade de Santiago de Compostela. Facultade de Medicina e Odontoloxía. Departamento de Medicina, 
K1 Proteína VGF
K1 TLQP-21
K1 Agonistas farmacológicos
K1 Prevención de la obesidad
AB VGF (non-acronymic) is a ~68 kDa neurosecretory protein, belongs to the extendedgranin family of proteins, initially identified as a nerve growth factor (NGF) induciblegene product, is selectively synthesised mostly in neuronal and neuroendocrine cells.Due to the presence of paired basic amino acid residues (R – Arginine, and K – Lysine),the VGF sequence undergoes endoproteolytic cleavage to produce several smallerpeptides, released upon stimulation via the regulated secretory pathway both in vitro andin vivo. There are data suggesting that the VGF-derived peptides are the biologicallyactive, stored in dense core vesicles and secreted in order to play a role in inter cellularcommunication, and responsible for the diverse range of biological functions associatedwith VGF. Several of these VGF-derived peptides have been characterised and areinvolved in energy balance, reproductive behaviour, pain modulation and mood order.Till now, the best characterized VGF derived peptide is designated as TLQP-21. Asgrowing data is accumulating on the several significant biological effects of TLQP-21like energy balance, pain modulation, gastric, reproduction, stress, diabetes;identification of its receptor(s) is of particular relevance. In light of this extensive arrayof effects, the very limited knowledge about its molecular mechanisms of TLQP-21 isremarkable. Recently, C3AR1 and gC1qR have been reported as receptors of murineTLQP-21. However, human TLQP-21 whose sequence shows differences with respect tomurine TLQP-21, exhibits at best very weak binding to these receptors, suggesting theexistence of different receptors for human vs rodent TLQP-21.Here using affinity chromatography and mass spectrometry-based protein identification,the heat shock cognate 71 kDa protein A8 (HSPA8) has been identified as a receptor ofhuman TLQP-21. Binding of TLQP-21 to membrane associated HSPA8 in live SHSY5Ycells was confirmed by cross-linking and FACS studies. Furthermore, molecularmodeling studies show that TLQP-21 can be docked into the peptide binding pocket ofHSPA8. The major task moving forward is to elucidate the signaling pathways of theligand TLQP-21 and its receptor HSPA8. Identification of HSPA8 as a receptor ofhuman TLQP-21 could open new approaches for diagnostics and therapeutics for a widerange of human diseases related with VGF, in particular those in which TLQP-21 hasbeen shown to have an effect.
YR 2015
FD 2015-09-15
LK http://hdl.handle.net/10347/13565
UL http://hdl.handle.net/10347/13565
LA eng
DS Minerva
RD 30 abr 2026