Non–Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice

Abstract Although isoforms of Ca2+/calmodulin-dependent protein kinase II (CaMKII) have been implicated in the regulation of gene expression in cultured cells, this issue has yet to be addressed in vivo. We report that the overexpression of calmodulin in ventricular myocytes of transgenic mice results in an increase in the Ca2+/calmodulin-independent activity of endogenous CaMKII. The calmodulin transgene is regulated by a 500-bp fragment of the atrial natriuretic factor (ANF) gene promoter which, based on cell transfection studies, is itself known to be regulated by CaMKII. The increased autonomous activity of CaMKII maintains the activity of the transgene and establishes a positive feedforward loop, which also extends the temporal expression of the endogenous ANF promoter in ventricular myocytes. Both the increased activity of CaMKII and transcriptional activation of ANF are highly selective responses to the chronic overexpression of calmodulin. These results indicate that CaMKII can regulate gene expression in vivo and suggest that this enzyme may represent the Ca2+-dependent target responsible for reactivation of the ANF gene during ventricular hypertrophy.

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Novel amino acid duplication in collagen XVII causes mild junctional epidermolysis bullosa by altering the coiled-coil structure and impairing collagen XVII trimerization and maturation

10.26226/morressier.595a9c53d462b80296c9f570 ◽

2017 ◽

Author(s):

Jasmin Kroeger

Keyword(s):

Amino Acid ◽

Epidermolysis Bullosa ◽

Coiled Coil ◽

Junctional Epidermolysis Bullosa ◽

Collagen Xvii ◽

Coil Structure

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Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs

The EMBO Journal ◽

10.1093/emboj/cdf532 ◽

2002 ◽

Vol 21 (19) ◽

pp. 5026-5035 ◽

Cited By ~ 142

Author(s):

Claus-Werner Franzke ◽

Kaisa Tasanen ◽

Heike Schäcke ◽

Zhongjun Zhou ◽

Karl Tryggvason ◽

...

Keyword(s):

Cell Surface ◽

Adhesion Protein ◽

Collagen Xvii

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Collagen XVII Is Destabilized by a Glycine Substitution Mutation in the Cell Adhesion Domain Col15

Journal of Biological Chemistry ◽

10.1074/jbc.275.5.3093 ◽

2000 ◽

Vol 275 (5) ◽

pp. 3093-3099 ◽

Cited By ~ 42

Author(s):

Kaisa Tasanen ◽

Johannes A. Eble ◽

Monique Aumailley ◽

Hauke Schumann ◽

Jens Baetge ◽

...

Keyword(s):

Cell Adhesion ◽

Collagen Xvii ◽

Glycine Substitution ◽

Substitution Mutation

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Bullous Pemphigoid Autoantibodies Preferentially Recognize Phosphoepitopes in Collagen XVII

Journal of Investigative Dermatology ◽

10.1038/jid.2008.132 ◽

2008 ◽

Vol 128 (11) ◽

pp. 2736-2739 ◽

Cited By ~ 11

Author(s):

Elena P. Zimina ◽

Silke C. Hofmann ◽

Anja Fritsch ◽

Johannes S. Kern ◽

Cassian Sitaru ◽

...

Keyword(s):

Bullous Pemphigoid ◽

Collagen Xvii

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Relationship between individual neuron and network spontaneous activity in developing mouse cortex

Journal of Neurophysiology ◽

10.1152/jn.00349.2014 ◽

2014 ◽

Vol 112 (12) ◽

pp. 3033-3045 ◽

Cited By ~ 6

Author(s):

Heather M. Barnett ◽

Julijana Gjorgjieva ◽

Keiko Weir ◽

Cara Comfort ◽

Adrienne L. Fairhall ◽

...

Keyword(s):

Normal Development ◽

Activity Patterns ◽

Piriform Cortex ◽

Intrinsic Excitability ◽

Intrinsic Activity ◽

Dorsal Cortex ◽

Synchronous Activity ◽

Mouse Cortex ◽

Propagating Waves ◽

Autonomous Activity

Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous central nervous system structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex, which participates in, but does not initiate, SSA (Lischalk JW, Easton CR, Moody WJ. Dev Neurobiol 69: 407–414, 2009). In this study, we used Ca2+ imaging of cultured embryonic day 18 to postnatal day 2 coronal slices (embryonic day 17 + 1–4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons was active asynchronously between waves, and a larger number of groups of coactive cells was present compared with the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained, while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation.

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