The distribution of murine 115-kDa epithelial microtubule-associated protein (E-MAP-115) during embryogenesis and in adult organs suggests a role in epithelial polarization and differentiation.
In interphase cells microtubules play fundamental roles in the intracellular distribution and movement of organelles and vesicles and thereby contribute to cellular polarization and differentiation. The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115) has been identified as a microtubule-stabilizing protein predominantly expressed in cell lines of epithelial origin. To assess a putative function of E-MAP-115 in epithelial morphogenesis in vivo, we have cloned the cDNA encoding the murine protein and studied the cellular distribution of E-MAP-115 mRNA and protein during murine embryogenesis and in adult organs. Analysis of the predicted amino acid sequence of murine E-MAP-115 revealed 81% sequence identity with its human homolog, the best-conserved part of the protein being the microtubule-binding site. Our data indicate that E-MAP-115 is expressed in several epithelia from 9.5 days of embryogenesis onwards and that its expression levels increase during development. From 14.5 days onwards, E-MAP-115 mRNA is found in some neuronal cells as well. In adult organs, E-MAP-115 is most abundant in epithelial cells of kidney tubules, in absorptive cells of the intestine and is widely distributed in the testis. E-MAP-115 expression correlates with the differentiation of certain epithelial cell types: in the adult intestine, for example, E-MAP-115 mRNA and protein are more abundant in the differentiating than in the proliferative cell compartment. Moreover, E-MAP-115 expression clearly correlates with the degree of cellular apicobasal polarity. In the developing kidney, E-MAP-115 mRNA is detected in the cuboidal cells of S-shaped bodies, of primitive tubules and glomerula, whereas, E-MAP-115 mRNA and protein are absent from mature podocytes which have lost their initial apico-basal polarity. The pattern of distribution of E-MAP-115 in vivo is so far unique for a MAP. Taken together, our results provide support for a role of E-MAP-115 in reorganizing the microtubule cytoskeleton during epithelial cell polarization and differentiation.
Fabre-Jonca
N
N
University of Geneva, Medical School, Switzerland.
Allaman
J M
JM
Radlgruber
G
G
Meda
P
P
Kiss
J Z
JZ
French
L E
LE
Masson
D
D
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D017124:Conserved Sequence; D018076:DNA, Complementary; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins