Regulation of cell polarity by controlled proteolytic systems

Epithelial and neuronal cells are highly asymmetric, with discrete regions responsible for different roles that underlie the generation of specific compartments within cells that are distinct in biochemical composition, structure, and morphology that ultimately lead to distinct functions. Controlled and specific molecular targeting and sorting have been studied to understand the generation of asymmetric domains inside cells. Recently, a new and complementary explanation has emerged to account for the generation of domains that are enriched by a subset of proteins or polarization determinants: local proteolysis. In this review, we discuss the most conspicuous proteolytic systems that may contribute to the generation of cell polarity, namely the ubiquitin-proteosome and the calpain systems. Specifically, we focus this review on two cellular processes that depend on the acquisition of cell polarity; cell migration and the establishment of an axon in a neuronal cell.

Triplets! Unexpected structural similarity among the three enzymes that catalyze initiation and termination of thyroid hormone effects

As três desiodases de iodotironinas catalisam a iniciação (D1, D2) e o término (D3) dos efeitos dos hormônios tiroideanos em vertebrados. Um modelo tridimensional concebido recentemente propõe que essas enzimas apresentam organização estrutural similar e pertençam à superfamília da thioredoxin (TRX)-fold. O sítio ativo é formado por um bolso contendo selenocisteína, definido pelos motivos b1-a1-b2 do TRX-fold, e um domínio similar ao sítio ativo da iduronidase, um membro do clan GH-A-fold das hidrolases de glicosídeos. Enquanto D1 e D3 são proteínas de meia-vida longa localizadas na membrana plasmática, a D2 é uma proteína residente do retículo endoplasmático com meia-vida de apenas 20min. A inativação da D2 é mediada por conjugação seletiva à ubiquitina, catalisada pela UBC-7, um processo que é acelerado pela catálise do T4, mantendo assim a homeostase local do T3. Além disso, a D2 interage e é substrato das VDU1 e VDU2 (pVHL-interacting deubiquitinating enzymes), fazendo com que sua desubiquitinação regule o suprimento de hormônio tiroideano ativo em células que expressam D2.

Activation of yeast trehalase by heat shock

1. Activation of Saccharomyces cerevisiae trehalase by heat shock was shown in all strains tested, including mutants in which the reponse to a glucose signal was absent. A low concentration of cAMP favored the response as seen in 2nd log cells or in ras2 and cyr1ts mutant strains. The heat shock effect upon trehalse activity was not observed under conditions of catabolite repession. 2 Neither hexokinase PII nor the heat shock protein hsp26 seemed to be involve in the axtivation of trehalase by heat shock. However, mutant strains deleted in the polyubiquitin gene showed only a 2-fold activation of the enzyme while in control strains a 5-to 7-fold irreversible activation was observed. 3. An alternative mechanism of trehalase activation by removal of an inhibitor through ligation with ubiquitin is discussed. Activation by cAMP-independent phosphorylation is also considered