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sorLA (Sorting protein-related receptor) is a type-1 membrane protein of unknown function that is expressed in neurons. Its homology to sorting receptors that shuttle between the plasma membrane, endosomes, and the Golgi suggests a related function in neuronal trafficking processes. Because expression of sorLA is reduced in the brain of patients with(More)
The GPI-anchored urokinase plasminogen activator receptor (uPAR) does not internalize free urokinase (uPA). On the contrary, uPAR-bound complexes of uPA with its serpin inhibitors PAI-1 (plasminogen activator inhibitor type-1) or PN-1 (protease nexin-1) are readily internalized in several cell types. Here we address the question whether uPAR is internalized(More)
We report that the Vps10p domain receptor sorLA binds the adaptor proteins GGA1 and -2, which take part in Golgi-endosome sorting. The GGAs bind with differential requirements via three critical residues in the C-terminal segment of the sorLA cytoplasmic tail. Unlike in sortilin and the mannose 6-phosphate receptors, the GGA-binding segment in sorLA(More)
alpha-Synuclein has been implicated in the pathogenesis of several neurodegenerative disorders based on the direct linking of missense mutations in alpha-synuclein to autosomal dominant Parkinson's disease and its presence in Lewy-like lesions. To gain insight into alpha-synuclein functions, we have investigated whether it binds neuronal proteins and(More)
SorLA/LR11 is a sorting receptor that regulates the intracellular transport and processing of the amyloid precursor protein (APP) in neurons. SorLA/LR11-mediated binding results in sequestration of APP in the Golgi and in protection from processing into the amyloid-beta peptide (Abeta), the principal component of senile plaques in Alzheimer's disease (AD).(More)
The subcellular localization of the alpha 2-macroglobulin receptor, also known as the low density lipoprotein receptor-related protein (LRP), was studied in postmortem human brain tissue by light and electron microscopic immunocytochemistry. A specific monoclonal antibody (A2MR2) against the extracellular alpha-chain of the molecule was utilized. Light(More)
The widespread deposition of amyloid plaques is one of the hallmarks of Alzheimer disease (AD). A recently described component of amyloid plaques is the 35-residue peptide, non-A beta component of AD amyloid, which is derived from a larger intracellular neuronal constituent, alpha-synuclein. We demonstrate that transglutaminase catalyses the formation of(More)
It has been reported that alpha 2-macroglobulin (alpha 2 M), known as a plasma protease inhibitor, promotes neurite outgrowth of cultured neurons from rat cerebral cortex. The neurons dissociated from 17-day embryonic (E17) rat cerebral cortex were cultured in the medium containing methylamine-modified alpha 2M labeled with fluorescein isothiocyanate (MA-(More)
Localization of the alpha 2 macroglobulin receptor (alpha 2MR) was studied in postmortem human brain tissue of Alzheimer disease (AD) and age-matched control cases with a monoclonal antibody (A2MR alpha 2) to the receptor. In control cases alpha 2MR was detected in neurons, glia, and some capillaries. Neuronal staining was most conspicuous in the(More)
The urokinase-type plasminogen activator receptor (uPAR) plays an important role on the cell surface in mediating extracellular degradative processes and formation of active TGF-beta, and in nonproteolytic events such as cell adhesion, migration, and transmembrane signaling. We have searched for mechanisms that determine the cellular location of uPAR and(More)