Demonstration of a role for α-synuclein as a functional microtubule-associated protein
2004
α-Synuclein is a major constituent of pathological intracellular inclusion bodies, a common feature of several neu- rodegenerative diseases. Two missense mutations in the α-synuclein gene have been identified in confirmed autosomal-dominant familial Parkinson's disease, which segregate with the illness. However, the physiological function of α-synuclein remains unknown. After biochemical investigations we have revealed tubulin to be an α-synuclein associated/binding protein. Here, we show that α-synuclein induces polymerization of purified tubulin into microtubules. Mutant forms of α-synuclein lose this potential. The binding site of α-synuclein to tubulin is identified, and co-localization of α-synuclein with microtubules is shown in cultured cells. To our knowledge, this is the first demonstration of microtubule-polymerizing activity of α-synuclein. Now we can see a striking resemblance between α-synuclein and tau: both have the same physiological function and pathological features, making abnormal structures in diseased brains known as synucleinopathies and tauopathies. The discovery of a physiological role for α-synuclein may provide a new dimension in researches into the mechanisms of α-synuclein-associated neurodegenerative diseases.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
28
References
158
Citations
NaN
KQI