Inositol 1,4,5-trisphosphate (IP3) is an intracellular second messenger that causes release of calcium from intracellular stores in response to signals sensed by receptors on the cell surface. One of the subtypes of receptors for IP3, IP3R1, is expressed predominantly in the brain and is important for motor functions and learning. The physiological roles of the other two, IP3R2 and IP3R3, which are widely expressed in mammalian tissues, have been unclear. Futatsugi et al. studied knockout mice lacking one or both proteins. The animals appeared to be similar at birth, but within 4 weeks, double-knockout animals lost weight and died. These animals had markedly impaired exocrine secretion in the salivary gland and pancreas, where these receptors have a key role in calcium signaling that regulates secretion.
A. Futatsugi, T. Nakamura, M. K. Yamada, E. Ebisui, K. Nakamura, K. Uchida, T. Kitaguchi, H. Takahashi-Iwanaga, T. Noda, J. Aruga, K. Mikoshiba, IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism. Science 309, 2232-2234 (2005). [Abstract] [Full Text]