Shahzadi Zarrin, Mukhopadhyay Chaitali
Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata, 700009, India.
J Membr Biol. 2017 Dec;250(6):617-627. doi: 10.1007/s00232-017-9987-5. Epub 2017 Sep 11.
Understanding the role of neural membrane in translocation and action of neurohormone is of great importance. Luteinizing hormone-releasing hormone (LHRH) is a neuropeptide hormone and it acts as a final signaling molecule by stimulating the synthesis of LH and FSH to maintain reproduction in all vertebrates. The receptors of LHRH are found in breast tumors and pituitary gland in the brain. Moreover, neural plasma membrane is also found to contain specific binding site for LHRH. The mechanism by which LHRH binds to membrane before it binds to the receptors is a very critical step and can have a profound impact upon the translation of peptide across the membrane. A complex form of glycosphingolipids known as Ganglioside is an important component of plasma membrane of nerve cells and breast tumor tissues. They play an important role in various physiological membrane processes. Therefore, the interaction of ganglioside-containing membrane with LHRH might be crucial in aiding the LHRH to translate through the neural membrane and reach its receptor for binding and activation. Using CD, UV-Absorbance, and fluorescence spectroscopy, the effect of Ganglioside Monosialo 1(GM1)-induced conformational changes of LHRH in the presence of Cholesterol (CHOL)/Sphingomyelin (SM) and GM1/CHOL/SM vesicles was studied. The aforesaid spectroscopic studies show that LHRH is able to bind with both the vesicles, but GM1-containing vesicles interact more effectively than vesicles without GM1. CHOL/SM vesicles partially disturb the conformation of the peptide. Moreover, binding of LHRH to GM1/CHOL/SM vesicles induces loss of conformational rigidity and attainment of a random coil.
了解神经膜在神经激素转运和作用中的作用非常重要。促黄体生成素释放激素（LHRH）是一种神经肽激素，它通过刺激促黄体生成素（LH）和促卵泡生成素（FSH）的合成，作为最终信号分子来维持所有脊椎动物的生殖功能。LHRH的受体存在于乳腺肿瘤和脑垂体中。此外，还发现神经质膜也含有LHRH的特异性结合位点。LHRH在与受体结合之前先与膜结合的机制是一个非常关键的步骤，可能会对肽跨膜转运产生深远影响。一种称为神经节苷脂的复杂糖鞘脂形式是神经细胞和乳腺肿瘤组织质膜的重要组成部分。它们在各种生理膜过程中发挥重要作用。因此，含神经节苷脂的膜与LHRH的相互作用可能对帮助LHRH穿过神经膜并到达其受体进行结合和激活至关重要。利用圆二色光谱（CD）、紫外吸收光谱和荧光光谱，研究了在胆固醇（CHOL）/鞘磷脂（SM）和GM1/CHOL/SM囊泡存在下，单唾液酸神经节苷脂1（GM1）诱导的LHRH构象变化的影响。上述光谱研究表明，LHRH能够与两种囊泡结合，但含GM1的囊泡比不含GM1的囊泡相互作用更有效。CHOL/SM囊泡会部分扰乱肽的构象。此外，LHRH与GM1/CHOL/SM囊泡的结合会导致构象刚性丧失并形成无规卷曲。
