Mechanisms of apical protein sorting in polarized thyroid epithelial cells.
The process leading to thyroid hormone synthesis is vectorial and depends upon the polarized organization of the thyrocytes into the follicular unit. Thyrocyte membrane proteins are delivered to two distinct domains of the plasma membrane using apical (AP) and basolateral (BL) sorting signals. A recent hypothesis for AP sorting proposes that apically destined proteins cluster with glycosphingolipids (GSLs) and cholesterol, into microdomains (or rafts) of the Golgi membrane from which AP vesicles originate. In MDCK cells the human neurotrophin receptor, p75hNTR, is delivered to the AP surface through a sorting signal, rich in O-glycosylated sugars, identified in its ectodomain. We have investigated whether this signal is functional in the thyroid-derived FRT cell line and whether p75hNTR clusters into lipid rafts to be sorted to the AP membrane. We found that p75hNTR is apically delivered via a direct pathway and does not associate with rafts during its transport to the surface of FRT cells. Therefore, although the same signal could be recognized by different cell types thyroid cells may possess a tissue-specific sorting machinery.
Centro di Endocrinologia ed Oncologia Sperimentale del CNR-Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, Naples, Italy.
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Lipardi
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Nitsch
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Zurzolo
D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D002784:Cholesterol / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D021382:Protein Sorting Signals; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*
D006028:Glycosphingolipids; D021382:Protein Sorting Signals; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D002784:Cholesterol