Sorting receptor SORLA: cellular mechanisms and implications for disease.
Vanessa Schmidt1, Aygul Subkhangulova2, Thomas E Willnow2,3
1Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Str. 10, 13125, Berlin, Germany. vanessa.schmidt@mdc-berlin.de.
Cellular and Molecular Life Sciences : CMLS
|November 11, 2016
Summary
Sorting-related receptor with A-type repeats (SORLA) directs cellular cargo, and its dysfunction causes diseases like Alzheimer's. This review explores SORLA's molecular sorting mechanisms and links genetic defects to severe human conditions.
Area of Science:
- Molecular biology
- Cell biology
- Genetics
Background:
- Sorting-related receptor with A-type repeats (SORLA) is a key intracellular sorting receptor.
- SORLA ensures proper cellular and tissue function by directing cargo proteins.
- Dysfunction of SORLA is implicated in major human diseases, including Alzheimer's disease, atherosclerosis, and obesity.
Purpose of the Study:
- To elucidate the molecular mechanisms governing SORLA and its cargo sorting.
- To examine SORLA's role in various cell types.
- To understand the link between genetic defects in SORLA and disease pathogenesis.
Main Methods:
- Literature review of molecular mechanisms.
- Analysis of SORLA sorting pathways.
- Examination of genetic defect consequences.
Main Results:
- SORLA sorts diverse cargo, including kinases, phosphatases, and signaling receptors.
- Specific molecular mechanisms control SORLA's intracellular trafficking.
- Genetic defects in SORLA lead to severe human diseases.
Conclusions:
- Understanding SORLA sorting is crucial for cellular and tissue homeostasis.
- SORLA dysfunction is a significant factor in the etiology of common human malignancies.
- Further research into SORLA mechanisms may reveal therapeutic targets for associated diseases.
Related Concept Videos
01:28Types of Receptors: Cell Surface Receptors
32.4K
Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are...
32.4K
01:15Receptor Downregulation in MVBs
2.9K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.9K
01:21Cell-surface Signaling
56.9K
Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
56.9K
01:15G Protein-coupled Receptors
18.8K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
18.8K
01:15G Protein-coupled Receptors
2.3K
2.3K
01:30Transducer Mechanism: G Protein–Coupled Receptors
6.6K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
6.6K