PARALEMMIN, A PRENYL-PALMITOYL-ANCHORED PHOSPHOPROTEIN ABUNDANT IN NEURONS AND IMPLICATED IN PLASMA-MEMBRANE DYNAMICS AND CELL PROCESS FORMATION

We report the identification and initial characterization of paralemmi n, a putative new morphoregulatory protein associated with the plasma membrane. Paralemmin is highly expressed in the brain but also less ab undantly in many other tissues and cell types. cDNAs from chicken, hum an, and mouse predict acidic proteins of 42 kD that display a pattern of sequence cassettes with high inter-species conservation separated b y poorly conserved linker sequences. Prenylation and palmitoylation of a COOH-terminal cluster of three cysteine residues confers hydrophobi city and membrane association to paralemmin. Paralemmin is also phosph orylated, and its mRNA is differentially spliced in a tissue-specific and developmentally regulated manner. Differential splicing, lipidatio n, and phosphorylation contribute to electrophoretic heterogeneity tha t results in an array of multiple bands on Western blots, most notably in brain. Paralemmin is associated with the cytoplasmic face of the p lasma membranes of postsynaptic specializations, axonal and dendritic processes and perikarya, and also appears to be associated with an int racellular vesicle pool. It does not line the neuronal plasmalemma con tinuously but in clusters and patches. Its molecular and morphological properties are reminiscent of GAP-43, CAP-23, and MARCKS, proteins im plicated in plasma membrane dynamics. Overexpression in several cell l ines shows that paralemmin concentrates at sites of plasma membrane ac tivity such as filopodia and microspikes, and induces cell expansion a nd process formation. The lipidation motif is essential for this morph ogenic activity. We propose a function for paralemmin in the control o f cell shape, e.g., through an involvement in membrane flow or in memb rane-cytoskeleton interaction.