Tau interacts with Golgi membranes and mediates their association with microtubules.
Tau, a microtubule-associated protein enriched in the axon, is known to stabilize and promote the formation of microtubules during axonal outgrowth. Several studies have reported that tau was associated with membranes. In the present study, we further characterized the interaction of tau with membranous elements by examining its distribution in subfractions enriched in either Golgi or endoplasmic reticulum membranes isolated from rat brain. A subfraction enriched with markers of the medial Golgi compartment, MG160 and mannosidase II, presented a high tau content indicating that tau was associated with these membranes. Electron microscope morphometry confirmed the enrichment of this subfraction with Golgi membranes. Double-immunogold labeling experiments conducted on this subfraction showed the direct association of tau with vesicles labeled with either an antibody directed against MG160 or TGN38. The association of tau with the Golgi membranes was further confirmed by immunoisolating Golgi membranes with an anti-tau antibody. Immunogold labeling confirmed the presence of tau on the Golgi membranes in neurons in vivo. Overexpression of human tau in primary hippocampal neurons induced the formation of large Golgi vesicles that were found in close vicinity to tau-containing microtubules. This suggested that tau could serve as a link between Golgi membranes and microtubules. Such role for tau was demonstrated in an in vitro reconstitution assay. Finally, our results showed that some tau isoforms present in the Golgi subfraction were phosphorylated at the sites recognized by the phosphorylation-dependent antibodies PHF-1 and AT-8.
Farah
Carole Abi
CA
Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Québec, Canada.
Perreault
Sébastien
S
Liazoghli
Dalinda
D
Desjardins
Mylène
M
Anton
Angela
A
Lauzon
Michel
M
Paiement
Jacques
J
Leclerc
Nicole
N
D000818:Animals; D001921:Brain / Q000648:ultrastructure; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000648:ultrastructure; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D016875:tau Proteins