p(HGNC:TRAK1) decreases p(HGNC:MAPT, pmod(Ph, Ser, 262))

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PubMed:22952452

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1.

Related Edges 12

• act(a(GO:mitochondrion)) positiveCorrelation p(HGNC:TRAK1)
• act(a(GO:mitochondrion)) positiveCorrelation p(HGNC:RHOT1)
• a(HBP:Neurodegeneration) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 262))
• p(HGNC:MAPT, pmod(Ph, Ser, 262)) positiveCorrelation a(HBP:Neurodegeneration)
• act(p(HGNC:MARK1), ma(kin)) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 262))
• p(HGNC:MARK1) negativeCorrelation p(HGNC:TRAK1)
• p(HGNC:MARK1) negativeCorrelation p(HGNC:RHOT1)
• p(HGNC:RHOT1) positiveCorrelation act(a(GO:mitochondrion))
• p(HGNC:RHOT1) decreases p(HGNC:MAPT, pmod(Ph, Ser, 262))
• p(HGNC:RHOT1) negativeCorrelation p(HGNC:MARK1)
• p(HGNC:TRAK1) positiveCorrelation act(a(GO:mitochondrion))
• p(HGNC:TRAK1) negativeCorrelation p(HGNC:MARK1)

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