The processing of Amyloid precursor protein (APP) is multifaceted, comprising of protein transport, internalization and sequential proteolysis. However, the exact mechanism of APP intracellular trafficking and distribution remains unclear. To determine the interaction between sortilin and APP and the effect of sortilin on APP trafficking and processing, we studied the binding site and its funct...

Here, we describe altered sorting of sortilin in adipocytes deficient for the σ1B-containing AP-1 complex, leading to the inhibition of adipogenesis. The AP-1 complex mediates protein sorting between the trans-Golgi network and endosomes. Vertebrates express three AP1 σ1 subunit isoforms - σ1A, σ1B and σ1C (also known as AP1S1, AP1S2 and AP1S3, respectively). σ1B-deficient mice display impaired...

Here, we describe altered sorting of sortilin in adipocytes deficient for the s1B-containing AP-1 complex, leading to the inhibition of adipogenesis. The AP-1 complex mediates protein sorting between the trans-Golgi network and endosomes. Vertebrates express three AP1 s1 subunit isoforms – s1A, s1B and s1C (also known as AP1S1, AP1S2 and AP1S3, respectively). s1B-deficient mice display impaired...

BACKGROUND Sortilin, a member of the Vps10p-domain receptor family, has been demonstrated a key regulator in mediating cellular response to pro-neurotrophins. In the present study, we investigated the role of sortilin in the apoptotic pathway of vascular smooth muscle cells. METHODS AND PRINCIPAL FINDINGS Immunohistochemistry revealed that sortilin was barely detectable in human and rat norma...

Aortic aneurysm and dissections account for 1% to 2% of all deaths in the Western countries, and the incidence of thoracic aortic aneurysm (TAA) is ≈10.4 per 100 000 personyears. Furthermore, because acute aortic dissections might be disguised as heart attacks, true incidence numbers could be significantly higher. Aortic aneurysms are categorized into 2 main groups depending on their location: ...

Sortilin is a multiligand sorting receptor responsible for the anterograde transport of lysosomal enzymes and substrates. Here we demonstrate that sortilin is also involved in retrograde protein traffic. In cultured 3T3-L1 adipocytes, sortilin together with retromer rescues Glut4 from degradation in lysosomes and retrieves it to the TGN, where insulin--responsive vesicles are formed. Mechanisti...