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Expression and Distribution of MAL2, an Essential Element of the Machinery for Basolateral-to-Apical Transcytosis, in Human Thyroid Epithelial Cells

Departamento de Endocrinología (M.M., M.A.G.-L.), Hospital de la Princesa, 28006 Madrid, Spain; and Centro de Biología Molecular "Severo Ochoa" (F.M-B., J.F.A., M.C.de.M., M.A.A.), Universidad Autónoma de Madrid and Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain

Address all correspondence and requests for reprints to: Miguel A. Alonso, Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. E-mail: maalonso{at}cbm.uam.es.

Polarized transport of newly synthesized proteins to the apical surface of epithelial cells takes place by a direct pathway from the Golgi or by an indirect route involving the delivery of the protein to the basolateral surface, followed by its endocytosis and transport across the cell. The indirect pathway, named transcytosis, is also used to translocate external material across the cell. MAL, a raft-associated integral membrane protein required for the direct apical route, is known to be expressed in the thyroid epithelium. MAL2, a member of the MAL protein family, has been recently identified as an essential component of the machinery for the transcytotic route in human hepatoma cells. Herein, we have investigated the expression and distribution of MAL2 in the human thyroid. MAL2 mRNA species were detected in the thyroid. Immunohistochemical analysis of thyroid follicles indicated that, in contrast to MAL, which predominantly distributed to the Golgi region, MAL2 distributed to the apical membrane. Biochemical analysis in primary thyrocyte cultures indicated that MAL2 exclusively resides in raft membranes. Confocal immunofluorescence analysis of thyrocyte cultures revealed that MAL2 predominantly localized in a subapical endosome compartment that was positive for Rab11a. Alterations in MAL2 expression, distribution, and appearance were found in specific types of follicular cell-derived carcinomas. Although the role of MAL2 has not been directly addressed in this study, the simultaneous expression of MAL and MAL2 suggests that traffic to the apical membrane in thyrocytes may rely on MAL for the direct route and on MAL2 for the transcytotic pathway.

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