EXISTENCE OF TRICHOHYALIN-KERATOHYALIN HYBRID GRANULES - COLOCALIZATION OF 2 MAJOR INTERMEDIATE FILAMENT-ASSOCIATED PROTEINS IN NON-FOLLICULAR EPITHELIA

Trichohyalin is a protein of relatively high molecular weight (similar to 200 kDa), associated with intermediate filaments, that was for man y years thought to be expressed only in the inner root sheath and medu lla of the hair follicle. We show here, however, that this protein is expressed in association with (pro)filaggrin in the granular layer of many non-follicular, keratinizing, stratified epithelia which also exp ress keratins K6/K16, including those of the filiform papillae of dors al tongue epithelia. In this epithelium, which elaborates morphologica lly heterogeneous keratohyalin granules in its upper cell layers, tric hohyalin forms hybrid granules with filaggrin, the major intermediate filament associated protein found in keratohyalin granules, which is n ormally expressed in advanced epidermal differentiation. These two int ermediate filament-associated proteins remain physically segregated in the hybrid granules, but they share the same fate, as they both becom e dispersed in transitional cells, and are undetectable in cornified c ells. Trichohyalin was also detected in nail matrix epithelia, the epi thelium of Hassal's corpuscles of the thymus, and newborn foreskin epi dermis. It is essentially absent from normal trunk and scalp epidermis , but is expressed in a few scattered cells of the granular layer that are also filaggrin-positive. In addition, trichohyalin is expressed i n the epidermis in a number of hyperplastic skin diseases. These findi ngs demonstrate that trichohyalin is not peculiar to a small number of hair follicle cells, but is expressed in a number of normal and patho logical epithelia where it is uniquely associated with filaggrin. In a ddition, since all these trichohyalin-expressing keratinocytes also sy nthesize keratins K6 and K16 (the markers for an ''alternative'' pathw ay of keratinocyte differentiation), this raises the possibility that the trichohyalin protein is specifically (or preferentially) involved in aggregating intermediate filaments containing the K6/K16 keratins.