Disease relevance of Sorl1

• These findings are compatible with function(s) of LR11 in neural organization and, possibly, pathogenesis of degenerative brain diseases [1].
• Differential expression of LR11 during proliferation and differentiation of cultured neuroblastoma cells [2].
• Here, we studied the proliferation-dependent expression of LR11 mRNA and protein using two cultured cell lines, IMR32 neuroblastoma and PC12 pheochromocytoma [2].

High impact information on Sorl1

• Release from cells and brain slices is stimulated by HA and by phorbol ester, and it is blocked by a metalloprotease inhibitor and by lowering the temperature to 20 degrees C. Blockade of SorLA shedding and treatment of cells with SorLA antisense oligonucleotides lead to a decrease in the rate of cell proliferation [3].
• HA enhances the translocation of SorLA from internal membranes to the cell surface and its internalization [3].
• Cell lines differ strongly in processing of SorLA, with NT2 cells expressing SorLA mainly as membrane receptor, whereas release predominates in BON cells [3].
• Transcripts of mSorLA were also detected outside the central nervous system in regions active in morphogenesis [4].
• During embryonic development mSorLA displayed a unique pattern of expression in the cerebral cortex, where a subpopulation of neurons was labeled before final differentiation [4].

Biological context of Sorl1

• Northern blot analysis revealed the highest abundance of mSorLA transcripts in the adult brain, lower levels in a variety of other organs and expression during embryogenesis [4].
• The possible involvement of LR11 in cellular proliferation and differentiation sheds new light on its functions in neurons, malignant, and vascular cells [2].

Anatomical context of Sorl1

• The predominant expression of LR11 in brain and the presence of elements found in neural adhesion molecules suggested a function(s) in the central nervous system (CNS) [1].
• In situ hybridization showed that neuronal bodies such as Purkinje cells in the cerebellum and other neurons in the hippocampal formations and the cerebral cortex are particularly rich in LR11 transcripts [1].
• SorLA was detected in intracellular vesicular structures, but not in the plasma membrane [5].

Other interactions of Sorl1

• The recent discovery of a novel mosaic LDLR family member by us (Yamazaki H., Bujo, H., Kusunoki, J., Seimiya, K., Kanaki, T., Morisaki, N., Schneider, W.J., and Saito, Y. (1996) J. Biol. Chem. 271, 24761-24768) and others, which we termed LR11, offers the opportunity to gain new insights into receptor multifunctionality [1].
• It shows homology to the mosaic receptor SorLA and the neurotensin receptor sortilin based on a common VPS10 domain which is the hallmark of this new receptor family [6].

References