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Leptin GroupPublications

Guidance of subcellular tubulogenesis by actin under the control of a synaptotagmin-like protein and Moesin.
Jayanandanan, N., Mathew, R. & Leptin, M.
Nat Commun. 2014 Jan 13;5:3036. doi: 10.1038/ncomms4036.
Apical membranes in many polarized epithelial cells show specialized morphological adaptations that fulfil distinct physiological functions. The air-transporting tubules of Drosophila tracheal terminal cells represent an extreme case of membrane specialization. Here we show that Bitesize (Btsz), a synaptotagmin-like protein family member, is needed for luminal membrane morphogenesis. Unlike in multicellular tubes and other epithelia, where it influences apical integrity by affecting adherens junctions, Btsz here acts at a distance from junctions. Localized at the luminal membrane through its tandem C2 domain, it recruits activated Moesin. Both proteins are needed for the integrity of the actin cytoskeleton at the luminal membrane, but not for other pools of F-actin in the cell, nor do actin-dependent processes at the outer membrane, such as filopodial activity or membrane growth depend on Btsz. Btsz and Moesin guide luminal membrane morphogenesis through organizing actin and allowing the incorporation of membrane containing the apical determinant Crumbs.
Europe PMC

Physical models of mesoderm invagination in Drosophila embryo.
Rauzi, M., Hocevar Brezavscek, A., Ziherl, P. & Leptin, M.
Biophys J. 2013 Jul 2;105(1):3-10. doi: 10.1016/j.bpj.2013.05.039.
The invagination of the mesoderm in the Drosophila melanogaster embryo is an intensely studied example of epithelial folding. Several theoretical studies have explored the conditions and mechanisms needed to reproduce the formation of the invagination in silico. Here we discuss the aspects of epithelial folding captured by these studies, and compare the questions addressed, the approaches used, and the answers provided.
Europe PMC

A role for Traf4 in polarizing adherens junctions as a prerequisite for efficient cell shape changes.
Mathew, S.J., Rembold, M. & Leptin, M.
Mol Cell Biol. 2011 Dec;31(24):4978-93. doi: 10.1128/MCB.05542-11. Epub 2011 Oct10.
Apical constriction of epithelial cells is a widely used morphogenetic mechanism. In the Drosophila embryo, the apical constrictions that internalize the mesoderm are controlled by the transcription factor Twist and require intact adherens junctions and a contractile acto-myosin network. We find that adherens junctions in constricting mesodermal cells undergo extensive remodeling. A Twist target gene encoding a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family, Traf4, is involved in this process. While TRAFs are best known for their functions in inflammatory responses, Traf4 appears to have a different role, and its mechanism of action is poorly understood. We show that Traf4 is required for efficient apical constriction during ventral furrow formation and for proper localization of Armadillo to the apical position in constricting cells. Traf4 and Armadillo interact with each other physically and functionally. Traf4 acts in a TNF receptor- and Jun N-terminal protein kinase (JNK)-independent manner to fine-tune the assembly of adherens junctions in the invaginating mesodermal cells.
Europe PMC

In Vivo Analysis of Ifn-{gamma}1 and Ifn-{gamma}2 Signaling in Zebrafish.
Aggad, D., Stein, C., Sieger, D., Mazel, M., Boudinot, P., Herbomel, P., Levraud, J.P., Lutfalla, G. & Leptin, M.
J Immunol. 2010 Dec 1;185(11):6774-82. Epub 2010 Nov 3.
The zebrafish genome contains a large number of genes encoding potential cytokine receptor genes as judged by homology to mammalian receptors. The sequences are too divergent to allow unambiguous assignments of all receptors to specific cytokines, and only a few have been assigned functions by functional studies. Among receptors for class II helical cytokines-i.e., IFNs that include virus-induced Ifns (Ifn-) and type II Ifns (Ifn-gamma), together with Il-10 and its related cytokines (Il-20, Il-22, and Il-26)-only the Ifn--specific complexes have been functionally identified, whereas the receptors for the two Ifn-gamma (Ifn-gamma1 and Ifn-gamma2) are unknown. In this work, we identify conditions in which Ifn-gamma1 and Ifn-gamma2 (also called IFNG or IFN-gamma and IFN-gammarel) are induced in fish larvae and adults. We use morpholino-mediated loss-of-function analysis to screen candidate receptors and identify the components of their receptor complexes. We find that Ifn-gamma1 and Ifn-gamma2 bind to different receptor complexes. The receptor complex for Ifn-gamma2 includes cytokine receptor family B (Crfb)6 together with Crfb13 and Crfb17, whereas the receptor complex for Ifn-gamma1 does not include Crfb6 or Crfb13 but includes Crfb17. We also show that of the two Jak2 paralogues present in the zebrafish Jak2a but not Jak2b is involved in the intracellular transmission of the Ifn-gamma signal. These results shed new light on the evolution of the Ifn-gamma signaling in fish and tetrapods and contribute toward an integrated view of the innate immune regulation in vertebrates.
Europe PMC