An intrinsic feed-forward mechanism for vertebrate gaze stabilization
نویسندگان
چکیده
transport; both proteins belong to the RND superfamily of proteins, originally defined by bacterial channel and transporter proteins involved in resistance, nodulation and division. These similarities have led to the suggestion that Ptc might function by transporting antagonists or agonists of Smo across the plasma membrane. Two lines of evidence have provided support for such roles of Ptc: in one study the secretion of pro-vitamin D3, which can act as an inhibitor of Smo, was shown to be promoted by Ptc activity. On the other hand, cholesterols and oxysterols have been shown to act as Smo agonists, prompting the suggestion that Ptc might regulate Smo by transporting these lipids away from Smo. Neither of these contrasting mechanisms addresses directly the control of Smo localisation by Ptc. Intriguingly, Ptc itself has now been found to shuttle to and from the primary cilia in response to Hh activity. In contrast to Smo, Ptc localises to the cilia in the absence of Hh signal, but is removed from them on binding to Hh. Thus, the primary cilia act not only as a centre for the regulation of the intracellular components of the pathway but also as a sensor for the extracellular ligand. The analysis of Hh signalling has given us many new insights into how cells sense and respond to signals and has illuminated our understanding of how such signals are deployed to generate cellular diversity during development. The sheer variety of its effects still poses important questions about the molecular basis of the differential response of cells to varying levels and duration of signalling activity and the nature of the differing competence of cells to respond to the same signal. Key unresolved issues include the biochemical function of Ptc and the way in which it regulates Smo activity as well as the role of the primary cilium in sensing and responding to the signal. Despite the novelties of Hh signalling, there are still some striking similarities between it and the other systems deployed by metazoans, most notably the Wnt pathway. In this respect, none of these signalling pathways seems unique; and the loss from nematodes of genes encoding key components of the Hh pathway — including Smo, SuFu and Fused— indicates that not all are indispensable for multicellular development.
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عنوان ژورنال:
- Current Biology
دوره 18 شماره
صفحات -
تاریخ انتشار 2008