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The limbic system-associated membrane protein (LAMP) selectively mediates interactions with specific central neuron
1Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854, USA.
Abstract:
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.