TRENDS in Cell Biology Vol.11 No.3 March 2001
http://tcb.trends.com 0962-8924/01/$ see front matter 2001 Elsevier Science Ltd. All rights reserved.
Getting a grip on cell migrationCell migration is a fundamental propertyof great importance in many cell-biological events during embryogenesisas well as in wound healing and tumourmetastasis. In all cell migration events,cells need to interact with the surrounding environment either through cellcell interactions or cellularinteractions with the extracellular matrix(ECM). A major group of receptors for the ECM are integrins, which areheterodimeric receptors comprisingnoncovalently associated and subunits. A number of integrins can share the same subunit, whereas the subunit confers integrin-specificproperties to a particular heterodimer. In integrin-mediatedevents, the cytoplasmic tails of the subunits have been shown to beimportant in both cell signalling and
cytoskeletal interactions. Integrin-specific effects also point to a role of thecytoplasmic tail of integrin chains. In an elegant study by Alahari et al., evidence is presented for molecularinteractions underlying the specific effects of 51.
Using a yeast two-hybrid screen withthe cytoplasmic tail of the integrin 5chain as a bait, a novel protein, namedNischarin (from Sanskrit, connotesslowness of motion), that interacts withthe integrin 5 chain was identified froman embryonic mouse expression library1.Overexpression of Nischarin in cellsresults in cytoskeletal rearrangements,reduced Rac signalling and reduced cellmigration. The integrin 5 chain isexpressed in a wide variety of cells, and,during early embryogenesis, 51 iscrucial for development of mesodermal
cells. Nischarin is highly expressed inneuronal tissues, indicating that proteins other than Nischarin mightinteract with 5 in non-neuronal tissuesand that Nischarin might have rolesindependent of its ability to interact with 51.
It will be most interesting to follow upthe studies of Nischarin to get a handle onhow Nischarin controls cell migration, and itis likely that more integrin -chain-specificproteins will be identified that will explainintegrin heterodimer-specific effects.
1 Alahari, S.K. et al. (2000) Nischarin, a novelprotein that interacts with the integrin5subunit and inhibits cell migration. J. Cell Biol.151, 11411154
At long last: identification of an oocyte mitogen receptorIt might come as a surprise that, despitethe profusion of receptor-focusedresearch and the keen interest of themedical community in understanding the intricacies of reproductive biology, a receptor responsible for activating oocyte meiotic maturation had not beendescribed in a single organism until theend of the year 2000. A Xenopus oocyteprogesterone receptor was recentlyidentified by two laboratories1,2,providing a handle for grasping a moredetailed and long-awaited molecularunderstanding of meiotic maturation.Moreover, this finding further supportsthe growing recognition of steroid-hormone receptors as mediators ofsignal-transduction pathways, in addition to their well-understood role as transcriptional regulators.
Progesterone clearly seems to act as a signal transducer in Xenopus oocytes,for, in this system, it acts at or near the cell surface by activating a signal-transduction pathway that, in the absence of transcription, results in oocyte maturation. It has thus beenhypothesized that progesterone actsthrough a novel receptor, rather thanthrough a conventional transcriptionfactor receptor. Two slightly different
Xenopus oocyte progesterone receptorscoined xPR1 and XPR-12 have now beendescribed, with XPR-1 being longer andcorresponding to the size of theendogenous receptor as judged bywestern blotting. There are minorvariations between the two, but, because neither study mentions thefindings of the other, the reader is left todiscern the true relationship betweenthem. Both contain well-conserved DNA-and ligand-binding domains, indicatingthat the oocyte progesterone receptor issimilar to the classical receptor. Thefinding that overexpression of xPR intissue-culture cells1 and XPR-1 in oocytes2 results in transcriptionalactivation of a reporter supports theconclusion that these receptors are indeed transcription factors. Curiously,without overexpression of XPR-1 inoocytes, progesterone treatment does not activate transcription from the samereporter, indicating the endogenousreceptor might be wired in ways that theoverexpressed version is not.
Although XPR-1 and xPR can act astranscriptional regulators, theirimportance in oocytes is revealed by their ability to render oocytes able torespond quicker and more sensitively to
progesterone. Importantly, blockingendogenous XPR-1 inhibits progesterone-induced maturation, which can bereversed by overexpressing either XPR-1 or the human progesteronereceptor2. Further support for a non-nuclear role is the finding that xPRcopurifies exclusively with the oocytecytosolic fractions1.
Despite the many unansweredquestions about how a steroid hormonereceptor activates a signal-transductionpathway, identification of the Xenopusoocyte progesterone receptor provides aconcrete means to address these questions. Hopefully, these studies are the first of many in which the receptors and cognate signaling pathways are to be unraveled in oocytes from differentspecies, including humans.
1 Bayaa, M. et al. (2000) The classical progesteronereceptor mediates Xenopus oocyte maturationthrough a non-genomic mechanism. Proc. Natl.Acad. Sci. U. S. A. 97, 1260712612
2 Tian, J. et al. (2000) Identification of XPR-1, aprogesterone receptor required for Xenopusoocyte activation. Proc. Natl. Acad. Sci. U. S. A.97, 1435814363