MICROFILAMENT-ASSOCIATED GROWTH CONE COMPONENT DEPENDS UPON TAU FOR ITS INTRACELLULAR-LOCALIZATION

We report here a novel intracellular localization and function of Tau proteins in cultured cerebellar neurons. Immunofluorescence staining o f detergent-extracted cytoskeletons with antibodies specific for Tau p roteins revealed intense labeling of growth cone microtubules. Besides , suppression of Tau by antisense oligonucleotide treatment results in the complete disappearance of antigen 13H9, a specific growth cone co mponent with properties of microfilament- and microtubule-associated p rotein [Goslin et al., 1989: J. Cell Biol. 109: 1621-1631], from its n ormal intracellular location. This phenomenon is unique to neurite-bea ring cells, is not associated with the disappearance of microtubules f rom growth cones, and is not reversed by taxol, a microtubule-stabiliz ing agent. In addition, Tau-suppressed neurons display a significant r eduction in growth cone area and fillopodial number; on the contrary, fillopodial length increases significantly. The alterations in growth cone morphology are accompanied by considerable changes in the phalloi din staining of assembled actin. Taken together, the present results s uggest that in developing neurons Tau proteins participate in mediatin g interactions between elements of the growth cone cytoskeleton import ant for maintaining the normal structural organization of this neuriti c domain. (C) 1994 Wiley-Liss, Inc.