Existence of trichohyalin-keratohyalin hybrid granules: co-localization of two major intermediate filament-associated proteins in non-follicular epithelia.

Trichohyalin is a protein of relatively high molecular weight (approximately 200 kDa), associated with intermediate filaments, that was for many years thought to be expressed only in the inner root sheath and medulla 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 express keratins K6/K16, including those of the filiform papillae of dorsal tongue epithelia. In this epithelium, which elaborates morphologically heterogeneous keratohyalin granules in its upper cell layers, trichohyalin forms hybrid granules with filaggrin, the major intermediate filament associated protein found in keratohyalin granules, which is normally expressed in advanced epidermal differentiation. These two intermediate filament-associated proteins remain physically segregated in the hybrid granules, but they share the same fate, as they both become dispersed in transitional cells, and are undetectable in cornified cells. Trichohyalin was also detected in nail matrix epithelia, the epithelium of Hassal's corpuscles of the thymus, and newborn foreskin epidermis. 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 in the epidermis in a number of hyperplastic skin diseases. These findings demonstrate that trichohyalin is not peculiar to a small number of hair follicle cells, but is expressed in a number of normal and pathological epithelia where it is uniquely associated with filaggrin. In addition, since all these trichohyalin-expressing keratinocytes also synthesize keratins K6 and K16 (the markers for an "alternative" pathway 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.