Carolyn L. Burek

University of Colorado Anschutz Medical Campus

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Jarred J. Bultema

University of Colorado Colorado Springs

Emily Anne Bates

University of Colorado Anschutz Medical Campus

Claire H Levitt

University of Colorado Denver

Richard K.P. Benninger

University of Colorado Anschutz Medical Campus

Santiago M. Di Pietro

Colorado State University

Yunus H. Ozekin

University of Colorado Anschutz Medical Campus

Mikaela L Follmer

University of Colorado Anschutz Medical Campus

Trevor J. Isner

University of Colorado Anschutz Medical Campus

Andrea L. Ambrosio

Sapienza University of Rome

Cooperative Institutions

University of Colorado Anschutz Medical Campus

University of Colorado Denver

Colorado State University

Collins College

The Medical Center of Aurora

University of California, Los Angeles

Instituto de Química y Fisicoquímica Biológicas

University of Colorado Colorado Springs

Karolinska Institutet

Karolinska University Hospital

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Depolarization induces calcium-dependent BMP4 release from mouse embryonic palate mesenchymal cells

Nature Communications (2024)

Mikaela L Follmer Trevor J. Isner Yunus H. Ozekin Claire H Levitt Carolyn L. Burek

Bone Morphogenetic Protein (BMP) signaling is essential for craniofacial development, though little is known about the mechanisms that govern BMP secretion. We show that depolarization induces calcium-dependent BMP4 release from mouse embryonic palate mesenchyme. We show endogenous transient changes in intracellular calcium occur in cranial neural crest cells, the cells from which embryonic palate mesenchyme derives. Waves of transient changes in intracellular calcium suggest that these cells are electrically coupled and may temporally coordinate BMP release. These transient changes in intracellular calcium persist in palate mesenchyme cells from embryonic day 9.5 to 13.5 mice. Disruption of a potassium channel called Kcnj2 significantly decreases the amplitude of calcium transients and the ability of cells to secrete BMP. Kcnj2 knockout mice have cleft palate and reduced BMP signaling. Our data suggest that temporal control of developmental cues is regulated by ion channels, depolarization, and intracellular calcium for mammalian craniofacial morphogenesis. BMP signaling is important for multiple process, including craniofacial development, but relatively little is known about how BMP ligands are secreted. Here they show that embryonic palate mesenchyme cells undergo transient changes in intracellular calcium and that depolarization of these cells induces BMP4 release, suggesting that ion channels are a node in BMP4 signaling.

10.1038/s41467-024-53642-2

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BLOC-2, AP-3, and AP-1 Proteins Function in Concert with Rab38 and Rab32 Proteins to Mediate Protein Trafficking to Lysosome-related Organelles

Journal of Biological Chemistry (2012)

Jarred J. Bultema Andrea L. Ambrosio Carolyn L. Burek Santiago M. Di Pietro

Melanosome

Rab

Organelle

Transport protein

10.1074/jbc.m112.351908

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Citations (117)