Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: effects on axonal viability.

Tau inclusions play a key role in the pathogenesis of tauopathies. Altered tau levels have been detected in retina and optic nerve of patients with glaucoma, suggesting the possibility of shared pathogenic mechanisms with tauopathies. Here we report that hyperphosphorylated transgenic tau accumulates in the nerve fibre layer and, from 2 months of age, aggregates into filamentous inclusions in retinal ganglion cells of human P301S tau transgenic mice.

Late onset distal axonal swelling in YFP-H transgenic mice.

Axonal swellings, or spheroids, are a feature of central nervous system (CNS) axon degeneration during normal aging and in many disorders. The direct cause and mechanism are unknown. The use of transgenic mouse line YFP-H, which expresses yellow-fluorescent protein (YFP) in a subset of neurons, greatly facilitates longitudinal imaging and live imaging of axonal swellings, but it has not been established whether long-term expression of YFP itself contributes to axonal swelling.

Functional analysis of AP-2 alpha and mu2 subunits.

The AP-2 adaptor complex plays a key role in cargo recognition and clathrin-coated vesicle formation at the plasma membrane. To investigate the functions of individual binding sites and domains of the AP-2 complex in vivo, we have stably transfected HeLa cells with wild-type and mutant small interfering RNA-resistant alpha and mu2 subunits and then used siRNA knockdowns to deplete the endogenous proteins. Mutating the PtdIns(4,5)P2 binding site of alpha, the phosphorylation site of mu2, or the YXXPhi binding site of mu2 impairs AP-2 function, as assayed by transferrin uptake.