SorLA regulates the activity of lipoprotein lipase by intracellular traffickingKlinger, S. C., Glerup, S., Raarup, M. K., Mari, M. C., Nyegaard, M., Koster, G., Prabakaran, T., Nilsson, S. K., Kjaergaard, M. M., Bakke, O., Nykjær, A., Olivecrona, G., Petersen, C. M. & Nielsen, M. S., 1-Apr-2011, In : Journal of Cell Science. 124, 7, p. 1095-105 11 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||11|
|Journal||Journal of Cell Science|
|Publication status||Published - 1-Apr-2011|
- Animals, Cattle, Cell Line, Cricetinae, Humans, Intracellular Space, LDL-Receptor Related Proteins, Lipoprotein Lipase, Membrane Transport Proteins, Protein Binding, Protein Structure, Tertiary, Protein Transport, RECEPTOR-ASSOCIATED PROTEIN, AMYLOID PRECURSOR PROTEIN, APOLIPOPROTEIN-A-V, VPS10P DOMAIN, CYTOPLASMIC DOMAIN, SORTING PROTEIN, ADIPOSE-TISSUE, MOUSE-BRAIN, BINDS, GENE
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