Regulation of microtubule-associated proteins, protein kinases and protein phosphatases during differentiation of SY5Y cells.
Regulation of expression and function of microtubule-associated proteins (MAPs) is critical for neurons to maintain normal cytoskeletal architecture and functions. We have shown previously that in differentiated human neuroblastoma SY5Y cells, the expression of tau, a major neuronal MAP, is dramatically increased, and tau phosphorylation is differentially regulated. In the present study, we investigated the expression, the subcellular distribution and the microtubule-binding activities of several MAPs in SY5Y cells upon differentiation. We also studied the activities of protein kinases and phosphatases that are involved in regulation of tau phosphorylation during cell differentiation. We found that the expression of MAP1b in addition to tau was upregulated upon differentiation. Tau, MAP1a, MAP1b and MAP2 had distinct immunocytochemical staining patterns in differentiated SY5Y cells, suggesting differential biological functions. The microtubule-binding activity of tau increased after cell differentiation, whereas the activities of MAP1a and MAP2 decreased. Upon differentiation, the phosphorylation of tau at Ser198/Ser199/Ser202 and Ser396/Ser404 was increased, but that at Ser262/Ser356 was decreased. These changes in tau phosphorylation were accompanied by an upregulation of activities of several protein kinases (cdk5, MAPK, PKC and CK-1) as well as protein phosphatases PP-1 and PP-2A. These results suggest that the expression, post-translational modifications and biological activities of various MAPs are differentially regulated to meet the biological needs during cell differentiation.
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA.
Niloufar
N
Haque
Cheng-Xin
CX
Gong
Amitabha
A
Sengupta
Khalid
K
Iqbal
Inge
I
Grundke-Iqbal
D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D008869:Microtubule-Associated Proteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D017239:Paclitaxel