Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA

Several mutations that cause severe forms of the human disease autosomal dominant retinitis pigmentosa cluster in the C-terminal region of rhodopsin. Recent studies have implicated the C-terminal domain of rhodopsin in its trafficking on specialized post-Golgi membranes to the rod outer segment of the photoreceptor cell. Here we used synthetic peptides as competitive inhibitors of rhodopsin trafficking in the frog retinal cell-free system to delineate the potential regulatory sequence within the C terminus of rhodopsin and model the effects of severe retinitis pigmentosa alleles on rhodopsin sorting. The rhodopsin C-terminal sequence QVS(A)PA is highly conserved among different species. Peptides that correspond to the C terminus of bovine (amino acids 324–348) and frog (amino acids 330–354) rhodopsin inhibited post-Golgi trafficking by 50% and 60%, respectively, and arrested newly synthesized rhodopsin in the trans-Golgi network. Peptides corresponding to the cytoplasmic loops of rhodopsin and other control peptides had no effect. When three naturally occurring mutations: Q344ter (lacking the last five amino acids QVAPA), V345M, and P347S were introduced into the frog C-terminal peptide, the inhibitory activity of the peptides was no longer detectable. These observations suggest that the amino acids QVS(A)PA comprise a signal that is recognized by specific factors in the trans-Golgi network. A lack of recognition of this sequence, because of mutations in the last five amino acids causing autosomal dominant retinitis pigmentosa, most likely results in abnormal post-Golgi membrane formation and in an aberrant subcellular localization of rhodopsin.

Risk factors for development of sexually abusive behaviour in sexually victimised adolescent boys: cross sectional study

Objective: To identify factors that may increase the risk of a sexually victimised adolescent boy developing sexually abusive behaviour.

Sex, sin and salvation : a case study of the narrative pictorial cycle of Saint Mary the Egyptian at Bourges Cathedral

This paper studies the narrative stained glass cycle of the Life of Saint Mary the Egyptian at Bourges Cathedral within the context of prevailing—and often conflicting--civil and ecclesiastical attitudes toward sex, sexual sin, and prostitution in early thirteenth century France. Although the Church maintained that sexual sin was mortal sin, civil records suggest the public was skeptical. Through the example of a penitent harlot, this window, both structurally and in thematic content, attempts to map a doctrinally appropriate path from sexual sin to purity of spirit—and salvation—through complete submission to the Church and its clergy.