Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The limbic system-associated membrane protein (LAMP) is a 64-68 x 10(3) M(r) glycoprotein that is expressed by subsets of neurons that are functionally interconnected. LAMP exhibits characteristics that are indicative of a developmentally significant protein, such as an early and restricted pattern of expression and the ability to mediate specific fiber-target interactions. A potential, selective adhesive mechanism by which LAMP may regulate the formation of specific circuits is investigated in the present experiments. LAMP is readily released from intact membranes by phosphatidyl inositol-specific phospholipase C. Purified, native LAMP, isolated by PI-PLC digestion and immunoaffinity chromatography, is capable of mediating fluorescent Covasphere aggregation via homophilic binding. To test the ability of LAMP to selectively facilitate substrate adhesion and growth of neurons from LAMP-positive, in contrast to LAMP-negative regions of the developing brain, purified LAMP was dotted onto nitrocellulose-coated dishes and test cells plated. Limbic neurons from perirhinal cortex bind specifically to substrate-bound LAMP within 4 hours, forming small cell aggregates with short neuritic processes that continue to grow through a 48 hour period of monitoring. Preincubation of cells with anti-LAMP has a modest effect on cell binding but significantly reduces initiation of process growth. Non-limbic neurons from somatosensory cortex and olfactory bulb fail to bind or extend processes on the LAMP substrate to any significant extent. All cell populations bind equally well and form neurites on poly-D-lysine and laminin. The present results provide direct evidence that LAMP can specifically facilitate interactions with select neurons in the CNS during development. The data support the concept that patterned expression of unique cell adhesion molecules in functionally related regions of the mammalian brain can regulate circuit formation.
 ...
PMID:The limbic system-associated membrane protein (LAMP) selectively mediates interactions with specific central neuron populations. 774 28

Neurotrimin (Ntm) together with the limbic system-associated membrane protein (LAMP) and the opioid-binding cell adhesion molecule (OBCAM) comprise the IgLON family of neural cell adhesion molecules. These glycosylphosphatidylinositol (GPI)-anchored proteins are expressed in distinct neuronal systems. In the case of Ntm, its expression pattern suggests a role in the development of thalamocortical and pontocerebellar projections (Struyket al., 1995). We have now characterized Ntm's function in cell adhesion and in neurite outgrowth. Cross-linking studies of transfected cells show that Ntm forms noncovalent homodimers and multimers at the cell surface. Ntm mediates homophilic adhesion, as evidenced by the reaggregation of the transfected cells and the specific binding of an Ntm-Fc chimera to these cells. Consistent with these results, Ntm-Fc binds to neurons that express Ntm at high levels, e.g., dorsal root ganglion (DRG) and hippocampal neurons. It does not bind to DRG neurons treated with phosphatidylinositol-specific phospholipase C (PI-PLC) or to sympathetic neurons that do not express Ntm or other members of the IgLON family at significant levels. Ntm promotes the outgrowth of DRG neurons, even after PI-PLC treatment, suggesting that its effects on outgrowth are mediated by heterophilic interactions. Of particular note, both membrane-bound and soluble Ntm inhibit the outgrowth of sympathetic neurons. These results strongly suggest that Ntm, and other members of the IgLON family, regulate the development of neuronal projections via attractive and repulsive mechanisms that are cell type specific and are mediated by homophilic and heterophilic interactions.
 ...
PMID:Neurotrimin mediates bifunctional effects on neurite outgrowth via homophilic and heterophilic interactions. 980 70

Opioid-binding cell adhesion molecule (OBCAM) is a member of the immunoglobulin superfamily containing limbic system-associated membrane protein (IgLON) subgroup of glycosylphosphatidylinositol-anchored immunoglobulin cell adhesion molecules. We have previously found that OBCAM is localized preferentially to dendrites compared with somata and terminals of hypothalamic vasopressin-secreting magnocellular neurons. This localization indicates that OBCAM is one of the dendrite-associated cell adhesion molecules. In the present study, we further characterized the localization and the sorting mechanism, and activity-dependent changes of this molecule in vasopressin-secreting magnocellular dendrites. Confocal microscopic observation revealed the preferential localization of OBCAM at the neurosecretory granules in the vasopressin-positive dendrites. Electron microscopic observation using chromogen-intensified and gold-conjugated methods also demonstrated the OBCAM labeling at most of the neurosecretory granules within the dendrites, while the labeling within the somata was observed at only a few neurosecretory granules. I.c.v. colchicine administration resulted in the disappearance of OBCAM immunoreactivity from the dendrites and in its concomitant accumulation at the somata, suggesting that OBCAM is synthesized at the somata and transported to the dendrites by dendrite-associated neurosecretory granules. During the postnatal development, OBCAM immunoreactivity targeted to vasopressin-positive dendrites became clear from at least 3 weeks after birth, although it appeared at only a few somata 2 weeks after birth. Phosphatidylinositol specific phospholipase C treatment of the membrane fraction of the supraoptic homogenate solubilized OBCAM. Kilon, another IgLON member, was also shown to localize at the neurosecretory granules of vasopressin-positive dendrites via the glycosylphosphatidylinositol anchor. High K(+)-stimulation appeared to cause the diffusion of OBCAM-labeled gold particles from neurosecretory granules together with the exocytosis. These findings indicate that OBCAM is synthesized within the somata, attached to vasopressin neurosecretory granules via the glycosylphosphatidylinositol anchor, and transported to the dendrites. Moreover, the subcellular localization of OBCAM is changed in an activity-dependent manner.
 ...
PMID:Dendrite-associated opioid-binding cell adhesion molecule localizes at neurosecretory granules in the hypothalamic magnocellular neurons. 1459 58