Sunday, August 9, 2009
Gene experession under the control of a fleck hippocampus
Hippocalcin (Hpca) is a Ca2+-binding protein of the neuronal calcium sensor (NCS) protein family that is predominantly expressed in the hippocampus. Hpca undergoes Ca2+ and myristoyl-dependent translocation from the cytosol to the intracellular membranes of the trans-Golgi network and the plasma membrane in response to an increase in Ca2+ concentration. Hpca may act as a multifunctional modulator in Ca2+-signaling pathways, such as those underlying long-lasting neural plasticity, neural excitability, neuronal cell death, and olfaction. Hpca is involved in the activity-dependent activation of the mitogen-activated protein kinase (MAPK) pathway through interactions with mixed-lineage kinases (MLKs), or by regulating extracellular signal-regulated kinase (ERK) signaling with subsequent activation of cAMP-response element-binding protein (CREB), which are key events in the gene expression system for long-lasting synaptic plasticity underlying learning and memory. Hpca-null mutant (Hpca-/-) mice have impaired spatial and associative learning abilities in the probe test on the Morris water maze and in a visual discrimination learning task. Hpca is implicated in hippocampal N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression (LTD) via binding to the β2-adaptin subunit of the AP2 adaptor complex, which mediates internalization of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor. The slow afterhyperpolarization current (IsAHP) activated by brief depolarization is not elicited in Hpca-/- hippocampal neurons, indicating that Hpca is an intermediary between Ca2+ influx and potassium channel activation. Hpca protects against Ca2+-induced cell death by interacting with neuronal apoptosis inhibitory protein (NAIP), diminishing endoplasmic reticulum (ER) stress, and up keeping Ca2+-extrusion. Hpca is also expressed in olfactory receptor neurons, and regulates the activities of ciliary adenylyl cyclases and particulate guanylyl cyclases in a Ca2+-dependent manner.
Alternative names for this molecule: BDR2; Calcium-binding protein BDR-2; Hippocalcin; Hpca; HPCA; Neuron specific calcium-binding protein hippocalcin; Neuron-specific calcium-binding protein hippocalcin