Age-related regulation of dendritic endocytosis associated with altered clathrin dynamics.
The protein composition of the neuronal plasma membrane is regulated by clathrin-mediated endocytosis and changes drastically over the neuronal lifespan. Here, we utilize the transition out of the period of early postnatal growth as a model system to study age-related changes in endocytosis. Previously, we have found that the dynamic behavior of endocytic clathrin coats in dendrites changes during this period, and that clathrin coat lifetime increases in older neurons. In this study, we examine endocytosis in neuronal dendrites by measuring transferrin (Tf) uptake, and find that it is markedly reduced in older neurons in culture. This decrease was not due to a reduction in transferrin receptor protein levels, nor to a decrease in the expression of endocytic proteins. However, imaging of endocytosis in living dendrites demonstrated that cargo transport through clathrin-coated pits was slower during internalization. Thus, endocytic function in dendrites is altered in older neurons, suggesting that as neurons age, protein trafficking mechanisms are controlled to complement maturational requirements.
Blanpied
Thomas A
TA
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Scott
Derek B
DB
Ehlers
Michael D
MD
D033965:Adaptor Protein Complex alpha Subunits / Q000378:metabolism; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D004268:DNA-Binding Proteins; D003712:Dendrites / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005333:Fetus; D034041:Monomeric Clathrin Assembly Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D033965:Adaptor Protein Complex alpha Subunits; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002966:Clathrin; D004268:DNA-Binding Proteins; C489536:Hip1 protein, mouse; D034041:Monomeric Clathrin Assembly Proteins; D010750:Phosphoproteins; D011990:Receptors, Transferrin; D014168:Transferrin; C439023:clathrin assembly protein AP180; D034281:Dynamins