Paired helical filaments (PHF) and abnormally phosphorylated tau

F. Molecular Cell Biolow of Neuronal FUNCTION

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PAIRED HELICAL FILAMENTS (PHF) AND ABNORMALLY PHOSPHORYLATED tau,

YASUO IHARA'. MASATO HASEGAWA',

MAHO MORISHIMA'. KOJI TAKIO'. Deuartment of 'Neuronatholoay. Institute of Brain Research. University of Tokyo. 7-3-l Hongo, Bunkvo-ku,

Tokyo 113, 'Laboratory for Aging

Process Research,

Frontier

Research Program. RIKEN. Wake, Saitama 351-01 Paired helical filaments (PHF) are a unit fibril of neurofibrillary tangles which are found in degenerating neurons in the Alzheimer's disease brain.

Although the major components of PHF were

identified as tau and ubiquitin, recent observations strongly suggest that tau composes a framework of PHF and ubiquitination is a secondary event. normal tau.

The tau forming PHF (PHF-tau) is distinct from

First, PHF-tau is recovered in the Sarkosyl-insoluble fraction.

Second, it shows an

unusually slow mobility on SDS-PAGE, suggesting that it is highly phosphorylated. phosphorylation insolubility.

is considered

to provide tau with

This abnormal

i.e. aggregation

and

We have attempted to determine the exact phosphorylation sites of PHF-tau by protein

sequencing together with LC/MS. site,

the unusual properties

PHF-tau appears to undergo distinct phosphorylation in the tau 1

the carboxy terminal portion, and additional two portions.

INVOLVEMENT OF ACTIN-LINKED MEMBRANE CYTOSKELETAL PROTEINS IN GROWTH CONE MOTILITY AND ADHESION KENJI SOBUE, Department of Neurochemistry and Neuropharmachology, Biomedical Research Center,Osaka University Medical School, Suits-shi,Osalca 565 The growth cone is a highly motile and adhesive structure, leading to maintain and promote neurite outgrowth. Using biochemical and immunocytochemical techniques, we investigated the regional distribution of membrane cytoskeletal proteins,

such as a-actinin

insensitive

a-actinin

and calspectin

which are the adhesive concentrated association involved

and calspectin

were observed

sites of growth

in the filopodia.

Therefore,

with the different functions in adhesiveness

of growth

(nonerythroid

spectrin

to localize

cone and neurite. three membrane

or fodrin),

to actin in the growth cone. Ca*‘-

in the growth cone body and the distal portion of neurites,

By contrast, cytoskeletal

of the growth cone substractures; cone, and Ca”-sensitive

in addition

a-actinin

in the adhesive Furthermore, we found the restricted location of pp60 ~~60’.“’ with the membrane cytoskeleton at the above sites.

Ca”-sensitive proteins

a-actinin

and actin were densely

show discrete differential

Ca”-insensitive

a-a&tin

distributions

and calspectin

and actin in Ca*‘-dependent sites of growth cone, suggesting

filopodial

in

may be motility.

the interaction

of