Semen and spermatozoa surface proteins (transglutaminase substrates)

• Report rights infringement
• published: 23 Apr 2016
• views: 20

http://webs.ono.com/fotgcren/index.htm http://webs.ono.com/programas/ Sexual intercourse is the major route of HIV transmission. More than 80% of HIV-1 infections are acquired through sexual intercourse (Münch 2007). Despite its dramatic spread in the human population, the efficiency of HIV-1 transmission via the sexual route is surprisingly poor (Münch 2007). Despite the growth and prevalence of the AIDS pandemic, HIV is an unexpectedly weak pathogen with low infectivity. In fact, it is estimated that less than 0.1% of viral particles are infectious in vitro, since infectivity is limited by low viral attachment rates to host cells. In vivo, HIV transmission is also inefficient, occurring as infrequently as 1 in every 200 to 2000 acts of sexual intercourse (Castellano 2012). A few HIV-1 particles are sufficient for spreading infection in the presence of an effective attachment factor (Münch 2007). SEMEN: Semen is the principal vehicle for the sexual transmission of HIV (Castellano 2012). Semen is the most important vector for HIV-1 transmission (Sabatte 2011). Globally, most infections result from genital exposure to semen (SE) of HIV-positive men (Münch 2007). Semen is the principal vehicle for the sexual transmission of HIV, and in vitro semen can enhance the infection of physiologically relevant cell types, including primary macrophages and CD4+ T cells. Thus, it was hypothesized that natural cofactors in seminal fluid could play a key role in HIV transmission by enhancing the efficiency of viral infectivity (Castellano 2012). SEMINAL PROTEINS: Semenogelins (SEMs) are proteins originating from the seminal vesicles that together with fibronectin comprise the major components of the semen coagulum. The SEM peptides are rich in lysine and arginine residues (Castellano 2012). How Tissue transglutaminase lysine sites are selected in substrate proteins? To study the amino acid residues influencing the amine donor substrate properties of lysines, Grootjans et al. and Groenen et al. have modified the native sequence around substrate lysine in αA-crystallin. Arginine had an enhancing effect. The size and charge of arginine exerted a positive effect (Csosz 2008). Semenogelin I and semenogelin II, the major gel-forming proteins in human semen, are substrates for transglutaminase (Peter 1998). SPERMATOZOA SURFACE PROTEINS: HIV-1 might exploit its ability to attach to the surface of the spermatozoa in order to improve infectivity (Sabatte 2011). gp120 & gp41 are two proteins (glycoproteins) located on the surface of Human immunodeficiency virus. They both are transglutaminase substrates (Mariniello 1993). TRANSGLUTAMINASE: We have investigated the presence of TGase activity in normal human semen (Porta 1986). Transglutaminase activity has been demonstrated in human semen, which may correspond to the prostate-specific transglutaminase (Peter 1998). TRANSGLUTAMINASE IN SEMINAL PLASMA A Ca2+-dependent, transglutaminase-like activity has been detected free in the human seminal plasma (Porta 1986). We report evidence of the ability of several seminal plasma proteins to act as acyl donor substrates for endogenous transglutaminase (Porta 1986). TRANSGLUTAMINASE ON THE SPERMATOZOON SURFACE A Ca2+-dependent, transglutaminase-like activity has been detected bound on the spermatozoon surface (Porta 1986). Human ejaculated spermatozoa have been shown to possess polyamine-binding sites specifically involved in transglutaminase-catalyzed reactions (Porta 1986). If the human transglutaminase substrates (e.g. the semenogelins or some of their fragments) also bind to spermatozoa after being cross-linked, or are actually cross-linked to the spermatozoa, it would be impossible to identify cross-linking products in seminal plasma after removal of the spermatozoa (Peter 1998). Due to the rapid degradation of semenogelins by PSA in vivo, it is possible that certain fragments of semenogelin formed upon digestion with PSA are the actual substrates for transglutaminase in human semen. Porta et al. observed that labelled spermidine, a naturally occurring polyamine in human semen, is incorporated into peptides of about 1018 kDa when added to dialysed liquefied human seminal plasma. These peptides could very well be fragments of semenogelins, formed during liquefaction, and thus suggesting that transglutaminase-mediated modifications of semenogelins and their fragments take place also in vivo (Peter 1998).