Retromer mediates a discrete route of local membrane delivery to dendrites.
A fundamental and still largely unresolved question is how neurons achieve rapid delivery of selected signaling receptors throughout the elaborate dendritic arbor. Here we show that this requires a conserved sorting machinery called retromer. Retromer-associated endosomes are distributed within dendrites in ∼2 μm intervals and supply frequent membrane fusion events into the dendritic shaft domain immediately adjacent to (<300 nm from) the donor endosome and typically without full endosome discharge. Retromer-associated endosomes contain β-adrenergic receptors as well as ionotropic glutamate receptors, and retromer knockdown reduces extrasynaptic insertion of adrenergic receptors as well as functional expression of AMPA and NMDA receptors at synapses. We propose that retromer supports a broadly distributed network of plasma membrane delivery to dendrites, organized in micron-scale axial territories to render essentially all regions of the postsynaptic surface within rapid diffusion distance of a local exocytic event.
Department of Psychiatry, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA.
Regina Wai-Yan
RW
Choy
Department of Psychiatry, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA.
Minjong
M
Park
Program in Cell Biology, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA.
Paul
P
Temkin
Department of Cellular & Molecular Pharmacology, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA.
Bruce E
BE
Herring
Department of Psychiatry, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA.
Aaron
A
Marley
Department of Cellular & Molecular Pharmacology, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA.
Roger A
RA
Nicoll
Department of Psychiatry, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA; Program in Cell Biology, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA; Department of Cellular & Molecular Pharmacology, University of California at San Francisco School of Medicine, San Francisco, CA 94158, USA. Electronic address: mark.vonzastrow@ucsf.edu.
Mark
M
von Zastrow
D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D003712:Dendrites / Q000378:metabolism*; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D046912:Multiprotein Complexes / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D009924:Organ Culture Techniques; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D046912:Multiprotein Complexes; D033921:Vesicular Transport Proteins; C562317:vacuolar protein sorting 35, rat