Sortilin is essential for proNGF-induced neuronal cell death
Anders Nykjaer1, Ramee Lee, Kenneth K Teng
1Department of Medical Biochemistry, Ole Worms Allé 170, Aarhus University, Gustav Wieds vej 10, DK-8000 Aarhus C, Denmark. an@biokemi.au.dk
Nature
|February 27, 2004
Summary
Sortilin acts as a co-receptor for pro-nerve growth factor (proNGF), binding to p75NTR. This interaction creates a signaling complex, making sortilin a molecular switch for proNGF-induced apoptosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Sortilin is a Vps10p-domain receptor found in various tissues, including the nervous system.
- While known to bind neurotensin, its prevalence in certain nervous system regions suggests other functions.
- Sortilin is expressed during embryogenesis in areas influenced by nerve growth factor (NGF) and its precursor, proNGF.
Purpose of the Study:
- To investigate the role of sortilin in neuronal development and signaling.
- To elucidate the mechanism by which proNGF induces apoptosis in p75NTR-expressing cells.
- To identify additional membrane proteins involved in proNGF-mediated cell death.
Main Methods:
- Investigated the interaction between proNGF, p75NTR, and sortilin.
- Characterized the formation of a signaling complex involving these proteins.
- Determined the functional role of sortilin in mediating proNGF-induced apoptosis.
Main Results:
- Sortilin forms a signaling complex by simultaneously binding to p75NTR and proNGF.
- Sortilin acts as a co-receptor for proNGF, specifically in conjunction with p75NTR.
- This complex formation is crucial for the induction of proNGF-mediated apoptosis.
Conclusions:
- Sortilin functions as a molecular switch that governs the pro-apoptotic signal initiated by proNGF via p75NTR.
- The findings reveal a novel mechanism for regulating programmed cell death in neuronal tissues.
- Sortilin's role as a co-receptor highlights its importance in neurotrophin signaling pathways.
Related Concept Videos
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...