Morpholino knockdown of the ubiquitously expressed transmembrane serine protease TMPRSS4a in zebrafish embryos exhibits severe defects in organogenesis and cell adhesion
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Anke Ohler
Abstract
Over the past years the members of the type II transmembrane serine protease (TTSP) family have emerged as new players in mammalian biology. TMPRSS4 (transmembrane protease/serine) is overexpressed in several human cancer tissues, promoting invasion, migration, and metastasis. However, the physiological function has not yet been elucidated. Here, we present morpholino knockdown studies targeting TMPRSS4a, a homolog of human TMPRSS4 in zebrafish embryos. By RT-PCR, we could demonstrate an expression of this protease already 5 h post-fertilization, suggesting important functions in the early stages of embryonic development. Indeed, in vivo gene silencing caused severe defects in tissue development and cell differentiation including a disturbed skeletal muscle formation, a decelerated heartbeat, and a degenerated vascular system. Scanning electron microscopy revealed strong defects in epidermal skin organization, with clearly altered cell-cell contacts, resulting in the detachment of keratinocytes from the underneath tissue. The disturbed organogenesis in general is consistent with RT-PCR results which exhibited a ubiquitous expression of TMPRSS4a, predominantly in kidney, skin, heart, and gills. Our results demonstrate the importance of TMPRSS4a in tissue development and cell differentiation. Whether its proteolytic activity is directed towards adhesion molecules or leads to the activation of other proteases needs to be investigated further.
©2011 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- GENES AND NUCLEIC ACIDS
- Sequence elements outside the catalytic core of natural hairpin ribozymes modulate the reactions differentially
- PROTEIN STRUCTURE AND FUNCTION
- Cooperative and independent activities of Sgt2 and Get5 in the targeting of tail-anchored proteins
- Novel neutrophil inhibitory factor homologue in the buccal gland secretion of Lampetra japonica
- MEMBRANES, LIPIDS, GLYCOBIOLOGY
- Generation of artificial channels by multimerization of β-strands from natural porin
- MOLECULAR MEDICINE
- Gender-related differences in the oxidant state of cells in Fanconi anemia heterozygotes
- CELL BIOLOGY AND SIGNALING
- Mesothelial cells activate the plasma kallikrein-kinin system during pleural inflammation
- Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes
- PROTEOLYSIS
- Morpholino knockdown of the ubiquitously expressed transmembrane serine protease TMPRSS4a in zebrafish embryos exhibits severe defects in organogenesis and cell adhesion
- NOVEL TECHNIQUES
- Isolation of dipeptidyl peptidase IV (DP 4) isoforms from porcine kidney by preparative isoelectric focusing to improve crystallization
