BIOLOGICAL OVERVIEW

Punt, along with Saxophone and Thick veins, constitute the Drosophila receptors for decapentaplegic. These receptors mediate the transduction of DPP signals into the cell. Mutations in these genes have the same effect as mutation in dpp, since without DPP's receptors, its signals fail to be communicated to the proper cells. The results are developmental confusion on a grand scale.

Decapentaplegic is responsible for induction of dorsal-ventral polarity in the fly. Loss of dpp through mutation yields catastrophic, indeed, topsy-turvy effects: the fly's back turns into its front. The back fails to develop normally and becomes instead a neurogenic ectoderm resembling tissue usually found in the ventral portion of the trunk.

Punt is homologous to a tumor growth factor (TGF-beta) receptor found in vertebrates. A digression to have a closer look at TGF-beta receptors is now in order. Much work has been carried out on TGF-beta receptors in vertebrates, providing detailed information on their nature and function. They have been classified into three types, non-descriptively named types I, II and III. Based on structural comparisons with the vertebrate TGF-beta receptors, Thick veins and Saxophone are homologous to type I and Punt to type II. Both receptor types are transmembrane proteins and their N-terminal domains are extracellular.

The TGF-beta receptor is really a heterodimer, consisting of both a type I and a type II receptor, each of which possess intracellular kinase domains. The kinase carries out the task of phosphorylation, a way of sending signals from one protein to another. A third subunit known as a type III receptor has a short cytoplasmic region lacking a kinase domain.

The type II receptor is essential for all known TGF-beta initiated signals. Homodimers of the type II and III receptors exist on the cell surface in the absence of TGF-beta. Type II and type III receptors interact in the presence of ligand. The type I receptors are also transmembrane serine-threonine kinases. Type II receptors require the corresponding type I receptor for signaling. Binding of TGF-beta or activin-A to type I receptors requires the presence of the corresponding type II receptor. Type I and type II receptors form heteromeric complexes after ligand binding (Lin, 1995 and references). The type II receptors act upstream of type I receptors, and so one may think ofthese components as primary receptors and transducers, respectively (Massagué, 1996).

Back to Punt: how then does Punt carry out its function? DPP binds to the extracellular domain of the heterodimer or heterotrimer DPP receptor. The DPP signal is transduced across the membrane activating the kinase function in the intracellular domain. The targets of the kinase function of Punt are not yet known. Phosphorylation of the type I receptor follows the DPP signal, in a transphosphorylation event carried out by the type II receptor. Phosphorylation activates the kinase activity of the type I receptor allowing it to transduce signals to unknown substrates (Wrana, 1994).

Punt is require for both SAX and TKV signaling. sax appears to be expressed more ubiquitously than thickveins, but paradoxically is required less ubiquitously than thick veins. SAX requires the function of both Thick veins and Punt to mediate signal transduction (Wharton, 1995, and Ruberte, 1995). Since sax is only necessary for the specification of the dorsalmost cell fate (amnioserosa) which requires the highest levels of DPP activity, SAX might serve as either part of the receptor complex or function independently to interpret peak levels of DPP.

Punt and Thickveins are both required for the establishment of dorsoventral polarity in the early embryo, the closure of the dorsal epidermis, and the correct formation of the visceral mesoderm and the tracheal system. All of these processes depend on DPP signaling (Ruperte, 1995 and Letsou, 1995).

PROTEIN STRUCTURE

Amino Acids - 488

Structural Domains and Evolutionary Homologies

The cysteine-rich extracellular domain contains three potential N-linked glycosylation sites. Most of the cytoplasmic region consists of a protein kinase domain. Two distinctive activin type II receptors and one TGF-beta type II receptor have been cloned from vertebrates, and each has a cytoplasmic protein-serine/threonine kinase domain, homologous to that of Punt. Another member of this receptor family is encoded by the C. elegans daf-1 gene, which controls larva development in response to an unknown ligand. There is also a Xenopus type II receptor homolog of Punt (Childs, 1993).

date revised: 27 MAY 97  

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