Mutations in the Drosophila hook gene inhibit endocytosis of the boss transmembrane ligand into multivesicular bodies.

Abstract

Abstract. Transmembrane ligands can be internalized across cell boundaries into receptor-expressing cells. In the developing Drosophila eye imaginal disc, the bride of sevenless transmembrane protein (boss) is expressed on the surface of R8 cells. After internalization into neighboring R7 cells, the boss protein accumulates in multivesicular bodies. In a search for genes that affect this cell-type-specific pattern of boss endocytosis, we found that mutations in the hook gene inhibit the accumulation of boss in multivesicular bodies of R7 cells~ In addition, hook flies exhibit pleiotropic phenotypes including abnormal bristle morphology and eye degeneration. The wild-type pattern of boss endocytosis was re- The term "juxtacrine signaling" has been proposed to describe the interaction between such transmembrane ligands and their receptors on adjacent cells (Bosenberg and Massague, 1993). The interaction between soluble ligands and their receptors is terminated by the internalization of the receptor/ligand complexes. In acidified endosomes, ligands are separated from their receptors and routed to lysosomes, where proteolysis terminates their life cycle (Gruenberg and Maxfield, 1995). The anchoring of complexes between transmembrane ligands and their receptors to both opposing plasma membranes raises the problem, how these complexes are removed from the cell surface. Analysis of the Drosophila bride of sevenless protein (boss) 1 indicates that internalization of transmembrane ligands across cell boundaries is one way by which cells terminate juxtacrine signaling (Cagan et al., 1992;Kr~imer, 1993 The boss protein functions as a neuronal inducer during the development of the compound eye in Drosophila (for review see Zipursky and Rubin, 1994). The ,--~800 ommatidia that compose the Drosophila eye initiate their development in the eye imaginal disc. Within this monolayer of polarized cells, the photoreceptor cells (R cells) of individual ommatidia emerge in a stereotyped pattern that is guided by cell-cell interactions (Tomlinson and Ready, 1987;Cagan, 1993). Neuronal development of the R7 cell is triggered by the activation of the sevenless receptor tyrosine kinase (sev) upon binding of its ligand, boss, a transmembrane protein containing seven membrane-spanning segments (Hart et al., 1990). The seven transmembrane domain of boss is required for its function. When the extracellular domain of boss was expressed as a soluble ligand, it antagonizes sev function instead of activating it (Hart et al., 1993).In the eye disc, boss is specifically expressed on the apical surface of R8 cells. Upon binding to the sev receptor, the boss ligand is internalized into R7 cells in a developmentally regulated process . In addition to R7, the R3 and R4 cells contact the boss-expressing R8 cell and present the sev receptor on their surface . Sev receptor expressed on the R3

Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed [URE3] prion variants

“…Btn2p is a member of the "Hook" family (49), whose founding member is a Drosophila gene involved in endocytosis (52). Cur1p does not show homology to metazoan Hook proteins but is similar to Btn2p (17).…”

Genetic Analysis of Lysosomal Trafficking inCaenorhabditis elegans

“…For example, the Hook family of proteins are present in Drosophila (Kramer and Phistry, 1996), C. elegans (Malone et al, 2003), and mammals but not in yeast (Walenta et al, 2001). The Drosophila Hook and human Hook1 proteins likely function in transport to lysosomes by mediating interactions between endosomal membranes and microtubules (Kramer and Phistry, 1996;Sunio et al, 1999;Richardson et al, 2004).…”

HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma

“…The C-terminal portion of HOOK3 binds to Golgi membranes in vitro, suggesting that it may participate in defining the organization and localization of the mammalian Golgi complex within the cell (Walenta et al 2001). Similar to all other family members, the HOOK3 protein contains an extended central coiled-coil motif, which was shown to mediate homodimerization in the Drosophila Hook protein (Kramer & Phistry 1996, Sevrioukov et al 1999). In the HOOK3-RET fusion, the first 11 exons of the HOOK3 gene are fused to exons 12-20 of the RET gene.…”