Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain

Marilyn Parra, Philippe Gascard, Loren D. Walensky, J. Aura Gimm, Seth Blackshaw, Nadine Chan, Yuichi Takakuwa, Trish Berger, Gloria Lee, Joel A. Chasis, Solomon H Snyder, Narla Mohandas, John G. Conboy

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Abstract

Brain-enriched isoforms of skeletal proteins in the spectrin and ankyrin gene families have been described. Here we characterize protein 4.1B, a novel homolog of erythrocyte protein 4.1R that is encoded by a distinct gene. In situ hybridization revealed high level, focal expression of 4.1B mRNA in select neuronal populations within the mouse brain, including Purkinje cells of the cerebellum, pyramidal cells in hippocampal regions CA1-3, thalamic nuclei, and olfactory bulb. Expression was also detected in adrenal gland, kidney, testis, and heart. 4.1B protein exhibits high homology to the membrane binding, spectrin-actin binding, and C-terminal domains of 4.1R, including motifs for interaction with NuMA and FKBP13. cDNA characterization and Western blot analysis revealed multiple spliceoforms of protein 4.1B, with functionally relevant heterogeneity in the spectrin-actin and NuMA binding domains. Regulated alternative splicing events led to expression of unique 4.1B isoforms in brain and muscle; only the latter possessed a functional spectrin-actin binding domain. By immunofluorescence, 4.1B was localized specifically at the plasma membrane in regions of cell-cell contact. Together these results indicate that 4.1B transcription is selectively regulated among neuronal populations and that alternative splicing regulates expression of 4.1B isoforms possessing critical functional domains typical of other protein 4.1 family members.

Original languageEnglish (US)
Pages (from-to)3247-3255
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number5
DOIs
StatePublished - Feb 4 2000

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Parra, M., Gascard, P., Walensky, L. D., Gimm, J. A., Blackshaw, S., Chan, N., Takakuwa, Y., Berger, T., Lee, G., Chasis, J. A., Snyder, S. H., Mohandas, N., & Conboy, J. G. (2000). Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain. Journal of Biological Chemistry, 275(5), 3247-3255. https://doi.org/10.1074/jbc.275.5.3247