Functional compartmentalization of endosomal trafficking for the synaptic delivery of AMPA receptors during long-term potentiation.
Endosomal membrane trafficking in dendritic spines is important for proper synaptic function and plasticity. However, little is known about the molecular identity and functional compartmentalization of the membrane trafficking machinery operating at the postsynaptic terminal. Here we report that the transport of AMPA-type glutamate receptors into synapses occurs in two discrete steps, and we identify the specific endosomal functions that control this process during long-term potentiation. We found that Rab11-dependent endosomes translocate AMPA receptors from the dendritic shaft into spines. Subsequently, an additional endosomal trafficking step, controlled by Rab8, drives receptor insertion into the synaptic membrane. Separate from this receptor delivery route, we show that Rab4 mediates a constitutive endosomal recycling within the spine. This Rab4-dependent cycling is critical for maintaining spine size but does not influence receptor transport. Therefore, our data reveal a highly compartmentalized endosomal network within the spine and identify the molecular components and functional organization of the membrane organelles that mediate AMPA receptor synaptic delivery during plasticity.
Brown
Tyler C
TC
Neuroscience Program and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Correia
Susana S
SS
Petrok
Cortney N
CN
Esteban
José A
JA
D000704:Analysis of Variance; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D011992:Endosomes / Q000378:metabolism*; D006177:Gynecomastia; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism*; D014170:Transformation, Genetic; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D008164:Luminescent Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020691:rab GTP-Binding Proteins