THE LIMBIC SYSTEM-ASSOCIATED MEMBRANE-PROTEIN (LAMP) SELECTIVELY MEDIATES INTERACTIONS WITH SPECIFIC CENTRAL NEURON POPULATIONS

The limbic system-associated membrane protein (LAMP) is a 64-68x10(3) Mr glycoprotein that is expressed by subsets of neurons that are funct ionally interconnected. LAMP exhibits characteristics that are indicat ive of a developmentally significant protein, such as an early and res tricted pattern of expression and the ability to mediate specific fibe r-target interactions. A potential, selective adhesive mechanism by wh ich LAMP may regulate the formation of specific circuits is investigat ed in the present experiments, LAMP is readily released from intact me mbranes by phosphatidyl inositol-specific phospholipase C. Purified, n ative LAMP, isolated by PI-PLC digestion and immunoaffinity chromatogr aphy,is capable of mediating fluorescent Covasphere aggregation via he mophilic binding. To test the ability of LAMP to selectively facilitat e substrate adhesion and growth of neurons from LAMP-positive, in cont rast to LAMP-negative regions of the developing brain, purified LAMP w as dotted onto nitrocellulose-coated dishes and test cells plated. Lim bic neurons from perirhinal cortex bind specifically to substrate-boun d LAMP within 4 hours, forming small cell aggregates with short neurit ic processes that continue to grow through a 48 hour period of monitor ing. Preincubation of cells with anti-LAMP has a modest effect on cell binding but significantly reduces initiation of process growth. Non-l imbic neurons from somatosensory cortex and olfactory bulb fail to bin d or extend processes on the LAMP substrate to any significant extent. All cell populations bind equally well and form neurites on poly-D-ly sine and laminin, The present results provide direct evidence that LAM P can specifically facilitate interactions with select neurons in the CNS during development. The data support the concept that patterned ex pression of unique cell adhesion molecules in functionally related reg ions of the mammalian brain can regulate circuit formation.