Tctex1 plays a key role in the α-synuclein autophagy lysosomal degradation pathway.

Tctex1 is an important structure of dynein light chain in mammalian cells, clarifying the role of Tctex1 in α-synuclein autophagy lysosomal degradation may offer insights into the formation of Lewy bodies and neuronal death. We constructed dsRED-N1-Tctex1 overexpression, pDsRED2-N1-Tctex1(T94E) mutation and transfected into SH-SY5Y cells. Relative protein expression was measured by Western Blot and mRNA levels were measured by real-time quantitative PCR. Confocal microscopy was used to observe their sublocalizations in cells. We found that: WST assay results show that cell activity decreased after Tctex1 mutation (T94E), while Tctex1 overexpression increased cell activity. In Tctex1 mutation transfected cell lines Tctex1 and dynein protein levels decreased; α-synuclein, LC3-II and LAMP2 protein increased. However, α-synuclein, LC3-II and LAMP2 proteins were reduced in Tctex1 overexpression cell lines, with the same trend was found in mRNA levels. In Tctex1 mutation transfected cell lines Tctex1 fluorescence intensity weakened; α-synuclein, LC3-II and LAMP2 fluorescence was enhanced, while α-synuclein, LC3-II and LAMP2 weakened in Tctex1 overexpressing cells. Our results suggest that Tctex1 mutants interference lead to Tctex1 downregulation and dysfunction. Tctex1 overexpression promoted autophagy lysosome fusion and effectively degraded α-synuclein with increased cell activity. Thus, Tctex1 plays an important role in α-synuclein autophagic degradation.