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FB2026_01
,
released March 12, 2026
The canonical role of the retromer complex is to rescue endosomal cargoes from lysosomal degradation and to redirect them to the Golgi or plasma membrane. Work in Drosophila has made use of mutations of Vps35 or Vps26 to compromise retromer function. Using Vps35 mutations, the role of neuronal retromer in the extracellular vesicles (EVs) pathway has been studied, with specific assessment of the fate of human APP (amyloid precursor protein) or the Drosophila ortholog Appl. Using Vps26 mutations assessed in larval salivary glands, it was found that transmembrane cargo proteins such as amyloid precursor protein (APP), which undergoes regulated exocytosis in larval salivary gland cells, are missorted to the endolysosomal system.
See also the human disease model report for Parkinson disease 17 (FBhh0000030), a form of Parkinson disease associated with retromer dysfunction.
[updated Jun. 2021 by FlyBase; FBrf0222196]
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from MIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Studies suggest that aberrant regulation of endosomal protein sorting and trafficking secondary to a dysfunction of the retromer complex may be implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease (Vagnozzi and Pratico, 2018; pubmed:30120416).
Retromer is a highly conserved multimeric protein complex present in all eukaryotic cells whose activity is essential for regulating the recycling and retrieval of numerous protein cargos from the endosome to trans-Golgi network or the cell surface (Vagnozzi and Pratico, 2018; pubmed:30120416).
High-scoring ortholog of human VPS35 (1 Drosophila to 1 human). Dmel\Vps35 shares 61% identity and 78% similarity with human VPS35.
High-scoring ortholog of human VPS26A and VPS26B (1 Drosophila to 2 human). Dmel\Vps26 shares 65-69% identity and 75-81% similarity with the human genes.