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Review
. 2022 Jan 3;11(1):148.
doi: 10.3390/cells11010148.

Endosomal Recycling Defects and Neurodevelopmental Disorders

Shinji Saitoh  1
Affiliations
Review

Endosomal Recycling Defects and Neurodevelopmental Disorders

Shinji Saitoh. Cells. .

Abstract

The quality and quantity of membrane proteins are precisely and dynamically maintained through an endosomal recycling process. This endosomal recycling is executed by two protein complexes: retromer and recently identified retriever. Defects in the function of retromer or retriever cause dysregulation of many membrane proteins and result in several human disorders, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Recently, neurodevelopmental disorders caused by pathogenic variants in genes associated with retriever were identified. This review focuses on the two recycling complexes and discuss their biological and developmental roles and the consequences of defects in endosomal recycling, especially in the nervous system. We also discuss future perspectives of a possible relationship of the dysfunction of retromer and retriever with neurodevelopmental disorders.

Keywords: Ritscher–Schinzel syndrome; Schaaf–Yang syndrome; endosomal recycling; retriever; retromer.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Schematic view of the endosome recycling system. Retromer and retriever complexes play a fundamental role in the recycling of numerous membrane proteins, although their target proteins are distinct. Retromer and retriever complexes interact with the WASH complex and the CCC complex for endosomal recycling (see text). WASH complex has an endosomal actin-remodeling function and is required for retromer and retriever to localize to the recycling endosome, while the CCC complex is shown to interact only with retriever.
Figure 2
Figure 2
Putative neurodevelopmental disorders associated with retromer and retriever complexes. Major clinical features are demonstrated for each disorder. ND, neurodevelopmental disorder; DD, developmental delay; ID, intellectual disability.
See this image and copyright information in PMC

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