Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 46, Pages 19927-19932Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1007381107
Keywords
calcium signaling; myogenic differentiation; Ned-19
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/D012694/1]
- Charite Rahel Hirsch
- BBSRC [BB/G008523/1, BB/D012694/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/G008523/1, BB/D012694/1] Funding Source: researchfish
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Calcium signaling is essential for the differentiation of many cell types, including skeletal muscle cells, but its mechanisms remain elusive. Here we demonstrate a crucial role for nicotinic acid adenine dinucleotide phosphate (NAADP) signaling in skeletal muscle differentiation. Although the inositol trisphosphate pathway may have a partial role to play in this process, the ryanodine signaling cascade is not involved. In both skeletal muscle precursors and C2C12, cells interfering with NAADP signaling prevented differentiation, whereas promoting NAADP signaling potentiated differentiation. Moreover, siRNA knockdown of two-pore channels, the target of NAADP, attenuated differentiation. The data presented here strongly suggest that in myoblasts, NAADP acts at acidic organelles on the recently discovered two-pore channels to promote differentiation.
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