The signaling protein CD38 is essential for early embryonic development.
CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity responsible for both the synthesis and the degradation of several Ca(2+)-mobilizing second messengers. Although a variety of functions have been ascribed to CD38, such as immune responses, insulin secretion, and social behavior in adults, nothing is known of its role during embryonic development when Ca(2+) signals feature prominently. Here, we report the identification and functional expression of CD38 from Xenopus laevis, a key model organism for the study of vertebrate development. We show that CD38 expression and endogenous ADP-ribosyl cyclase activity are developmentally regulated during cellular differentiation. Chemical or molecular inhibition of CD38 abolished ADP-ribosyl cyclase activity and disrupted elongation of the anterior-posterior axis and differentiation of skeletal muscle, culminating in embryonic death. Our data uncover a previously unknown role for CD38 as an essential regulator of embryonic development.
Department of Cell and Developmental Biology, University College London, Anatomy Building, Gower Street, London WC1E 6BT, United Kingdom.
Dev
D
Churamani
Timothy J
TJ
Geach
Latha
L
Ramakrishnan
Nicole
N
Prideaux
Sandip
S
Patel
Leslie
L
Dale
D051997:ADP-ribosyl Cyclase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000201:enzymology*; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology / Q000201:enzymology; D014982:Xenopus laevis
D051997:ADP-ribosyl Cyclase 1; D002118:Calcium