Nuclear and cytoplasmic tau proteins from human nonneuronal cells share common structural and functional features with brain tau

The heterogeneous family of tau proteins interacts with microtubules, actin filaments, and intermediate filaments. The tau isoforms have been shown to play a major role in neuronal polarity. However, tau-like proteins have be en found in several other types of cells. Previous studies have also indica ted the presence of a nuclear tau. The relationships between nuclear and cy toplasmic tau as well as the functional aspects of the nuclear tau are unkn own. In this study, we demonstrate by reverse transcriptase polymerase chai n reaction using specific primers that a transcript with features of neuron al tau is present in human fibroblast and Huh-7 hepatoma cell lines. Additi onally, we present the first isolation and characterization of cytosolic an d nuclear tau-like proteins from nonneuronal cells. Nonneuronal cytosolic t au components were isolated using the perchloric acid precipitation approac h, while nuclear tau was isolated after selective extractions using high-io nic strength buffers. The cytoplasmic tau of nonneuronal cells is composed of at least three isoforms, whereas two main isoforms were detected in nucl ear tau. Interestingly, the cytoplasmic and nuclear tau components exhibite d the capacity to promote tubulin polymerization in vitro. Immunofluorescen ce studies using monoclonal anti-tau antibodies indicated a discrete distri bution of tau protein in both the interphase and mitotic nucleus. In the la tter, tau colocalized with the chromosomal scaffold. These studies, togethe r With previous evidence on tau roles in modulating microtubule growth from centrosomes, and its role in the interaction patterns that stabilize the i ntegrity of the cytoskeletal network, strongly support the idea that tau is a multifunctional protein involved in fundamental cellular processes. (C) 2000 Wiley-Liss, Inc.