SorLA regulates the activity of lipoprotein lipase by intracellular trafficking
2011 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 124, 1095-1105 p.Article in journal (Refereed) Published
Many different tissues and cell types exhibit regulated secretion of lipoprotein lipase (LPL). However, the sorting of LPL in the trans Golgi network has not, hitherto, been understood in detail. Here, we characterize the role of SorLA (officially known as SorLA-1 or sortilin-related receptor) in the intracellular trafficking of LPL. We found that LPL bound to SorLA under neutral and acidic conditions, and in cells this binding mainly occurred in vesicular structures. SorLA expression changed the subcellular distribution of LPL so it became more concentrated in endosomes. From the endosomes, LPL was further routed to the lysosomes, which resulted in a degradation of newly synthesized LPL. Consequently, an 80% reduction of LPL activity was observed in cells that expressed SorLA. By analogy, SorLA regulated the vesicle-like localization of LPL in primary neuronal cells. Thus, LPL binds to SorLA in the biosynthetic pathway and is subsequently transported to endosomes. As a result of this SorLA mediated-transport, newly synthesized LPL can be routed into specialized vesicles and eventually sent to degradation, and its activity thereby regulated.
Place, publisher, year, edition, pages
2011. Vol. 124, 1095-1105 p.
Intracellular trafficking, Lipoprotein lipase, SorLA (SORL1), Vps10p-domain receptor
Medical and Health Sciences
Research subject Physical Chemistry
IdentifiersURN: urn:nbn:se:umu:diva-40820DOI: 10.1242/jcs.072538PubMedID: 21385844OAI: oai:DiVA.org:umu-40820DiVA: diva2:403026