Human immunoglobulins and Fc fragments promote microtubule assembly via tau proteins and induce conformational changes of neuronal microtubules in vitro.
The influence of human immunoglobulins (Ig) in neuronal cytoskeleton stability was studied in vitro. Here we show that human Ig and Fc fragments stimulate animal and human microtubule assembly by binding to microtubules via tau isoforms. In presence of Ig, microtubules show increased aggregation, twisting and rigidity. Non-immune Ig and Fc fragments promote microtubule assembly in temperature-dependent manner and stabilize microtubules at a molecular ratio of 1 Ig per 4 tubulin dimers. These in vitro data provide an experimental support for an immuno-mediated modulation of the cytoskeleton. In conjunction with previous neuropathological data, they suggest that Ig could participate in early stages of neurodegeneration by affecting the microtubule stability in vivo.
Riederer
Irène M
IM
Institut de Biologie Cellulaire et de Morphologie, Faculté de Médecine, Université de Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
Pfulg
Claudine
C
Bouras
Constantin
C
Giannakopoulos
Panteleimon
P
Riederer
Beat M
BM
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002417:Cattle; D002540:Cerebral Cortex / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D019281:Dimerization; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism / Q000494:pharmacology*; D007136:Immunoglobulins / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D009024:Morphogenesis / Q000187:drug effects; D009410:Nerve Degeneration / Q000276:immunology*; D011487:Protein Conformation; D013552:Swine; D016875:tau Proteins / Q000502:physiology*
D003598:Cytoskeletal Proteins; D007141:Immunoglobulin Fc Fragments; D007136:Immunoglobulins; D016875:tau Proteins