Zanin Juan Pablo, Unsain Nicolás, Anastasia Agustin
Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA.
Instituto de Investigación Médica Mercedes y Martin Ferreyra, (INIMEC-CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.
J Neurochem. 2017 May;141(3):330-340. doi: 10.1111/jnc.13993. Epub 2017 Mar 21.
Most growth factors and hormones are synthesized as pre-pro-proteins which are processed to the biologically active mature protein. The pre- and prodomains are cleaved from the precursor protein in the secretory pathway or, in some cases, extracellularly. The canonical functions of these prodomains are to assist in folding and stabilization of the mature domain, to direct intra and extracellular localization, to facilitate storage, and to regulate bioavailability of their mature counterpart. Recently, exciting evidence has revealed that prodomains of certain growth factors, after cleaved from the precursor pro-protein, can act as independent active signaling molecules. In this review, we discuss the various classical functions of prodomains, and the biological consequences of these pro-peptides acting as ligands. We will focus our attention on the brain-derived neurotrophic factor prodomain (pBDNF), which has been recently described as a novel secreted ligand influencing neuronal morphology and physiology.
大多数生长因子和激素最初合成时是前体-前体蛋白，经过加工后成为具有生物活性的成熟蛋白。前结构域和前体结构域在分泌途径中从前体蛋白上切割下来，在某些情况下，是在细胞外切割。这些前体结构域的典型功能是协助成熟结构域的折叠和稳定，指导细胞内和细胞外定位，促进储存，并调节其成熟对应物的生物利用度。最近，令人兴奋的证据表明，某些生长因子的前体结构域从前体前体蛋白上切割下来后，可以作为独立的活性信号分子发挥作用。在这篇综述中，我们讨论了前体结构域的各种经典功能，以及这些前体肽作为配体的生物学后果。我们将把注意力集中在脑源性神经营养因子前体结构域（pBDNF）上，它最近被描述为一种影响神经元形态和生理的新型分泌配体。
