Mid-range Ca 2+ signaling occurs downstream of SOCE and uses ER tunnels to transport Ca 2+ to specific effectors without inducing a global cytosolic Ca 2+ rise (Ca 2+ teleporting/tunneling). We have recently described a novel Ca 2+ signaling module that allows Ca 2+ signaling in the mid-range spatially, between the classically defined Ca 2+ micro-domain and global Ca 2+ signals that cover the entire cell. We are investigating the mechanisms controlling this specificity by focusing on the SOCE pathway and IP 3-dependent Ca 2+ release. This specificity is encoded in part in the spatial and temporal features of Ca 2+ signals to activate subsets of downstream effectors leading to a defined cellular response. We are also investigating the regulation of Ca 2+ signaling pathways at the cellular level in various pathological conditions and cell types, including vascular smooth muscle cells in hypertension breast cancer metastasis and the role of Ca 2+ signaling in regulating metabolism.Ĭa 2+ signals often lead to different cellular responses in the same cell. We are interested in the complex interplay between these Ca 2+ signaling modules and effectors in the context of meiosis progression. Ca 2+ signaling remodeling affects both Ca 2+ release and influx pathways including the IP 3 receptor, the store-operated Ca 2+ entry, the plasma membrane Ca 2+ ATPase, and the Ca 2+–activated Cl- channels (CaCC). Ca 2+ signaling differentiation during oocyte maturation allows the egg to produce the specialized Ca 2+ transient at fertilization to initiate egg activation. Ca 2+ is the universal signal for egg activation at fertilization and for mediating the egg–to–embryo transition.
Fully grown oocytes in the ovary are not fertilizable until they undergo oocyte maturation, which encompasses both entry into meiosis, and a cytoplasmic differentiation that includes a dramatic remodeling of the Ca 2+signaling machinery. In fact, Ca 2+signaling is often remodeled during cellular development and cellular pathology. Oocyte maturation in preparation for fertilization offers a classical example of remodeling of calcium signaling during development. We are particularly interested in Ca 2+ signaling as a ubiquitous signaling module throughout phylogeny that is critical in mediating cellular responses to various cues. We are fascinated by the regulation of intracellular signaling pathways under both physiological and pathological conditions in the context of the regulation of oocyte maturation, meiotic arrest, cell cycle progression and secretion.