Molecular interaction of α-synuclein with tubulin influences on the polymerization of microtubule in vitro and structure of microtubule in cells.
Microtubule dynamics is essential for many vital cellular processes such as in intracellular transport, metabolism, and cell division. Evidences demonstrate that α-synuclein may associate with microtubular cytoskeleton and its major component, tubulin. In the present study, the molecular interaction between α-synuclein and tubulin was confirmed by GST pull-down assay and co-immunoprecipitation. The interacting regions within α-synuclein with tubulin were mapped at the residues 60-100 of α-synuclein that is critical for the binding activity with tubulin. Microtubule assembly assays and sedimentation tests demonstrated that α-synuclein influenced the polymerization of tubulin in vitro, revealing an interacting region-dependent feature. Confocal microscopy detected that exposures of α-synuclein proteins inhibited microtubule formation in the cultured cells, with a length-dependent phenomenon. Our data highlight a potential role of α-synuclein in regulating the microtubule dynamics in neurons. The association of α-synuclein with tubulin may further provide insight into the biological and pathophysiological function of synuclein.
Zhou
R M
RM
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing, 100052, People's Republic of China.
Huang
Y X
YX
Li
X L
XL
Chen
C
C
Shi
Q
Q
Wang
G R
GR
Tian
C
C
Wang
Z Y
ZY
Jing
Y Y
YY
Gao
C
C
Dong
X P
XP
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D006224:Cricetinae; D006801:Humans; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009391:Nephelometry and Turbidimetry; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D011817:Rabbits; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012996:Solutions; D014162:Transfection; D014404:Tubulin / Q000302:isolation & purification / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
D050505:Mutant Proteins; D011994:Recombinant Proteins; C497604:SNCA protein, human; D012996:Solutions; D014404:Tubulin; D051844:alpha-Synuclein