Unconventional Protein Secretion of Keratin 75 by Ameloblasts In Vivo

The study investigated the presence and secretion of Keratin-75 (K75) in enamel tissue, particularly in ameloblasts, and found that K75, unlike typical cytokeratins, was secreted extracellularly with enamel matrix proteins (EMPs) by secretory stage ameloblasts. The research confirmed K75's presence in ameloblasts, stratum intermediate, and enamel matrix using in situ hybridization, immunofluorescence, and mass spectrometry. K75 was found in large granular bodies and vesicles, overlapping with EMPs ameloblastin and amelogenin. The study also revealed that K75 utilized a novel unconventional protein secretion pathway involving the ER-Golgi-Intermediate-Compartment (ERGIC) and Golgi, despite lacking a signal peptide, marking the first discovery of such a pathway for a cytosolic cytokeratin.