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Endosomal retrieval and recycling of integral cargo proteins is essential for cell and organism development and homeostasis and is orchestrated through a specialised endosomal nanodomain, the retrieval sub-domain. Sub-domain dysfunction is associated with human disease, but our mechanistic understanding of its function remains poorly described. Here, using proximity proteomics of retrieval sub-domain components Retromer and Retriever we identify mechanistic details of retrieval sub-domain composition and organization, including an unrecognised complexity in the interface with RAB GTPase switching. Combining X-ray crystallography and in silico predictions with biochemical and cellular analysis, we reveal that Retromer directly associates and recruits the RAB10 regulators DENND4A, DENND4C, TBC1D1, and TBC1D4, and the RAB35 regulator TBC1D13 to regulate retrieval sub-domain function. The retrieval sub-domain therefore constitutes a hub for integrating cargo recycling with the regulated switching of selected RAB GTPases. We propose this constitutes a major component of the neuroprotective role of the retrieval sub-domain.
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http://dx.doi.org/10.1038/s41467-025-61802-1 | DOI Listing |
Nat Commun
July 2025
School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol, UK.
Endosomal retrieval and recycling of integral cargo proteins is essential for cell and organism development and homeostasis and is orchestrated through a specialised endosomal nanodomain, the retrieval sub-domain. Sub-domain dysfunction is associated with human disease, but our mechanistic understanding of its function remains poorly described. Here, using proximity proteomics of retrieval sub-domain components Retromer and Retriever we identify mechanistic details of retrieval sub-domain composition and organization, including an unrecognised complexity in the interface with RAB GTPase switching.
View Article and Find Full Text PDFFront Psychol
March 2025
Seymour Fox School of Education, The Hebrew University of Jerusalem, Jerusalem, Israel.
Background: Previous research showed that having older, typically developing (TD) siblings is associated with better social functioning in autistic children. Modeling by older siblings and the fact that siblings provide a social companion to practice social skills were suggested as explanations.
Objectives: To investigate whether having older autistic siblings is associated with a similar or an opposite pattern.
Genes (Basel)
October 2023
William F. Connell School of Nursing, Boston College, Chestnut Hill, MA 02476, USA.
In the 20 years since the initial sequencing of the human genome, genomics has become increasingly relevant to nursing. We sought to chart the current state of genomics in nursing by conducting a systematic scoping review of the literature in four databases (2012-2022). The included articles were categorized according to the Cochrane Collaboration outcome domains/sub-domains, and thematic analysis was employed to identify key topical areas to summarize the state of the science.
View Article and Find Full Text PDFTraffic
December 2023
Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India.
In hepatocytes, the Wilson disease protein ATP7B resides on the trans-Golgi network (TGN) and traffics to peripheral lysosomes to export excess intracellular copper through lysosomal exocytosis. We found that in basal copper or even upon copper chelation, a significant amount of ATP7B persists in the endolysosomal compartment of hepatocytes but not in non-hepatic cells. These ATP7B-harbouring lysosomes lie in close proximity of ~10 nm to the TGN.
View Article and Find Full Text PDFJ Telemed Telecare
April 2025
Institute of Public and Preventive Health, Augusta University, Augusta, GA, USA.
Although the use of audiovisual telemedicine has grown in recent years especially during recent COVID-19-related lockdowns, evidence shows there is still a lack of tools that can be used for the assessment of telemedicine encounters. The few validated questionnaires that are available for assessing telemedicine encounters are not often used. Non-validated questionnaires dominate research, leading to results that cannot be compared or extrapolated to other research or medical sites.
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