1. Academic Validation
  2. TLQP-21, A VGF-Derived Peptide Endowed of Endocrine and Extraendocrine Properties: Focus on In Vitro Calcium Signaling

TLQP-21, A VGF-Derived Peptide Endowed of Endocrine and Extraendocrine Properties: Focus on In Vitro Calcium Signaling

  • Int J Mol Sci. 2019 Dec 24;21(1):130. doi: 10.3390/ijms21010130.
Elena Bresciani 1 Roberta Possenti 2 Silvia Coco 1 Laura Rizzi 1 Ramona Meanti 1 Laura Molteni 1 Vittorio Locatelli 1 Antonio Torsello 1
Affiliations

Affiliations

  • 1 School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
  • 2 Department of Systems Medicine, University of Roma Tor Vergata, 00133 Roma, Italy.
Abstract

VGF gene encodes for a neuropeptide precursor of 68 kDa composed by 615 (human) and 617 (rat, mice) residues, expressed prevalently in the central nervous system (CNS), but also in the peripheral nervous system (PNS) and in various endocrine cells. This precursor undergoes proteolytic cleavage, generating a family of Peptides different in length and biological activity. Among them, TLQP-21, a peptide of 21 Amino acids, has been widely investigated for its relevant endocrine and extraendocrine activities. The complement complement C3a receptor-1 (C3aR1) has been suggested as the TLQP-21 receptor and, in different cell lines, its activation by TLQP-21 induces an increase of intracellular CA2+. This effect relies both on CA2+ release from the endoplasmic reticulum (ER) and extracellular CA2+ entry. The latter depends on stromal interaction molecules (STIM)-Orai1 interaction or transient receptor potential channel (TRPC) involvement. After CA2+ entry, the activation of outward K+-Ca2+-dependent currents, mainly the KCa3.1 currents, provides a membrane polarizing influence which offset the depolarizing action of CA2+ elevation and indirectly maintains the driving force for optimal CA2+ increase in the cytosol. In this review, we address the main endocrine and extraendocrine actions displayed by TLQP-21, highlighting recent findings on its mechanism of action and its potential in different pathological conditions.

Keywords

KCa3.1 current; TLQP-21; VGF; calcium (Ca2+); calcium release-activated calcium channel (CRAC)-Orai1; complement C3a receptor-1 (C3aR1); endocrine; extraendocrine; stromal interaction molecules (STIM); transient receptor potential channel (TRPC).

Figures
Products