We deduced the structure of the mouse profilin II gene. It contains five exons that can generate four different transcripts by alternative splicing. Two transcripts encode different profilin II isoforms (designated IIa and IIb) that have similar affinities for actin but different affinities for polyphosphoinositides and proline-rich sequences. Profilins IIa and IIb are also present in humans, suggesting that all mammals have three profilin isoforms. Profilin I is the major form in all tissues, except in the brain, where profilin IIa is most abundant. Profilin IIb appears to be a minor form, and its expression is restricted to a limited number of tissues, indicating that the alternative splicing is tightly regulated. Western blotting and whole-mount in situ hybridization show that, in contrast to the expression of profilin I, the expression level of profilin IIa is developmentally regulated. In situ hybridization of adult brain sections reveals overlapping expression patterns of profilins I and IIa.Changes in both cell shape and motility in response to extracellular signals require mechanical forces from the actin cytoskeleton. The formations of lamellipodia, focal contacts, the contractile ring during cytokinesis, and neuronal growth cone motility depend on the controlled polymerization-depolymerization of actin filaments (7,40). The regulation of these processes is accomplished by many actin binding proteins that act at different points in time and space, depending on the extracellular signals (44).Profilin is a small, ubiquitous actin binding protein, thought to be a key regulatory of actin dynamics in living cells (8,41). In vitro experiments have shown that profilin acts as an actin monomer-sequestering protein when barbed ends of filaments are capped (e.g., by gelsolin). When the capping protein is removed, polymerization of actin can occur, and actin-profilin complexes can add to the fast-growing ends, thereby enhancing actin polymerization in the presence of thymosin ␤4 (22, 34).Profilin can bind other molecules including phosphatidylinositol 4,5-bisphosphate (PIP 2 ) (28) and proline-rich domains of several proteins like the vasodilator-stimulated phosphoprotein (VASP), Enabled (Ena), mammalian Ena (Mena), aczonin, the Wiskott-Aldrich syndrome protein (WASP), its neural homologue N-WASP, and mammalian Diaphanous (p140mDia) (1,2,13,38,45,46,48). In lower eukaryotes, many other proline-rich proteins have been identified as profilin ligands, such as formin-homology proteins (47). The actinrelated protein-2/3 complex (Arp2/3 complex), composed of seven different polypeptides, was originally identified as a profilin binding complex (29).Until 1993, only one profilin isoform was known to be present in mammalian cells. Honoré and coworkers (20) discovered a second profilin gene in a random cDNA cloning project. The open reading frame predicted a protein with a high similarity to profilin I (62.1% identity), and therefore the protein was designated profilin II. Northern blot analysis showed that the expression l...

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We deduced the structure of the mouse profilin II gene. It contains five exons that can generate four different transcripts by alternative splicing. Two transcripts encode different profilin II isoforms (designated IIa and IIb) that have similar affinities for actin but different affinities for polyphosphoinositides and proline-rich sequences. Profilins IIa and IIb are also present in humans, suggesting that all mammals have three profilin isoforms. Profilin I is the major form in all tissues, except in the brain, where profilin IIa is most abundant. Profilin IIb appears to be a minor form, and its expression is restricted to a limited number of tissues, indicating that the alternative splicing is tightly regulated. Western blotting and whole-mount in situ hybridization show that, in contrast to the expression of profilin I, the expression level of profilin IIa is developmentally regulated. In situ hybridization of adult brain sections reveals overlapping expression patterns of profilins I and IIa.