Profilin II Is Alternatively Spliced, Resulting in Profilin Isoforms That Are Differentially Expressed and Have Distinct Biochemical Properties

Abstract

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.

ACKNOWLEDGMENTS

Anja Lambrechts and Attila Braun contributed equally to this paper.

We thank F. Van Roy for use of the DNA sequencing facility for some of the profilin clones. We acknowledge Leen Van Troys for critically reading the manuscript and Griet Vandeweghe and Daniel Broekaert for assistance with additional experiments. Part of this work was carried out in the laboratory of Frank Gertler (Massachusetts Institute of Technology, Cambridge), and we acknowledge his contribution.

A.L. was the recipient of a travel grant from the Fund for Scientific Research-Flanders (FWO-Vlaanderen, Belgium) to work at MIT. C.A. is a research associate of the Fund for Scientific Research-Flanders. This work was supported by grants G004497, G006096, and G022598 of the Fund for Scientific Research-Flanders to C.A. and J.V.; a grant from the “Geneeskundige Stichting Koningin Elisabeth” to C.A.; GOA grants 12051296 and 120C1797 to J.V.; and a grant of the Swedish Cancer Foundation to R.F.

ADDENDUM IN PROOF

A paper describing the profilin II gene structure and the alternative splice variants profilins IIa and IIb by Di Nardo et al. is in press in J. Cell. Sci. The nomenclature used for the two profilin isoforms is the same as in this paper.