Expression of Specific Isoforms of Protein 4.1 in Erythroid and Non-Erythroid Tissues

  • Tang K. Tang
  • Thomas L. Leto
  • Vincent T. Marchesi
  • Edward J. BenzJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 34)


Protein 4.1 in red cells is an important submembrane linking protein that binds to spectrin actin complexes at one end of its structure and to transmembrane proteins, such as glycophorin, at the other. Protein 4.1 thus contributes to the strength and flexibility of the erythrocyte membrane, a fact dramatically exemplified by the appearance of hereditary hemolytic anemias in patients with absent or abnormal protein 4.1. Recently, protein 4.1 forms have been discovered in many non-erythroid tissues. Their intracellular locations raise the possibility that these isoforms might have different functions. We have thus conducted comparative analysis of erythroid and non-erythroid protein 4.1 forms by cloning and sequencing erythroid and lymphoid protein 4.1 cDNAs. The lymphoid protein 4.1 isoforms exhibit at least five nucleotide sequence motifs that appear to be either inserted or deleted relative to the erythroid mRNA sequence by alternative splicing of a common mRNA precursor. One of these motifs, located within the spectrin-actin binding domain, is found only in erythroid cells and is specifically produced during erythroid cell maturation. The selective expression of this alternatively spliced mRNA during erythroid maturation implies the existence of a lineage specific splicing mechanism whose activity is triggered by terminal maturation. Two motifs alter the 5’ untranslated region of the “prototypical” erythroid mRNA in such a way as to permit synthesis of a novel larger isoform. This form appears to localize preferentially in the nucleus. We thus conclude that a single gene gives rise to multiple protein 4.1 isoforms with potentially diverse locations and functions.


Erythroid Cell Rabbit Reticulocyte Lysate Actin Binding Domain Globin Gene Expression Isolate cDNA Clone 
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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Tang K. Tang
    • 1
    • 2
    • 3
  • Thomas L. Leto
    • 1
    • 2
    • 3
  • Vincent T. Marchesi
    • 1
    • 2
    • 3
  • Edward J. BenzJr.
    • 1
    • 2
    • 3
  1. 1.Department of Internal MedicineYale University School of MedicineNew HavenUSA
  2. 2.Department of Human GeneticsYale University School of MedicineNew HavenUSA
  3. 3.Department of PathologyYale University School of MedicineNew HavenUSA

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