Sac3

Summary

Gene Symbol: Sac3
Description: FIG4 phosphoinositide 5-phosphatase
Alias: A530089I17Rik, AI326867, Sac3, polyphosphoinositide phosphatase, FIG4 homolog, SAC domain-containing protein 3, Sac domain-containing inositol phosphatase 3, phosphatidylinositol 3,5-bisphosphate 5-phosphatase
Species: mouse
Products:     Sac3

Top Publications

  1. Chow C, Zhang Y, Dowling J, Jin N, Adamska M, Shiga K, et al. Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. Nature. 2007;448:68-72 pubmed
    ..Positional cloning identified insertion of ETn2beta (early transposon 2beta) into intron 18 of Fig4 (A530089I17Rik), the homologue of a yeast SAC (suppressor of actin) domain PtdIns(3,5)P2 5-phosphatase located in the ..
  2. Yan Q, Guo J, Zhang X, Bai Y, Wang L, Li J. Trauma does not accelerate neuronal degeneration in Fig4 insufficient mice. J Neurol Sci. 2012;312:102-7 pubmed publisher
    ..Taken together, our results demonstrate that haploinsufficiency of fig4 does not impose risks in rodents to develop neuronal degeneration in either naïve or traumatic conditions. ..
  3. Campeau P, Lenk G, Lu J, Bae Y, Burrage L, Turnpenny P, et al. Yunis-Varón syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase. Am J Hum Genet. 2013;92:781-91 pubmed publisher
    ..Our results describe a role for PI(3,5)P(2) signaling in skeletal development and maintenance. ..
  4. Ferguson C, Lenk G, Meisler M. Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2. Hum Mol Genet. 2009;18:4868-78 pubmed publisher
    ..These results establish a role for PI(3,5)P(2) in autophagy in the mammalian central nervous system (CNS) and demonstrate that mutations affecting PI(3,5)P(2) can contribute to inclusion body disease. ..
  5. Katona I, Zhang X, Bai Y, Shy M, Guo J, Yan Q, et al. Distinct pathogenic processes between Fig4-deficient motor and sensory neurons. Eur J Neurosci. 2011;33:1401-10 pubmed publisher
    ..These two distinct pathological changes may contribute to neuronal degeneration. ..
  6. Lenk G, Ferguson C, Chow C, Jin N, Jones J, Grant A, et al. Pathogenic mechanism of the FIG4 mutation responsible for Charcot-Marie-Tooth disease CMT4J. PLoS Genet. 2011;7:e1002104 pubmed publisher
    CMT4J is a severe form of Charcot-Marie-Tooth neuropathy caused by mutation of the phosphoinositide phosphatase FIG4/SAC3. Affected individuals are compound heterozygotes carrying the missense allele FIG4-I41T in combination with a null ..
  7. Zolov S, Bridges D, Zhang Y, Lee W, Riehle E, Verma R, et al. In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P. Proc Natl Acad Sci U S A. 2012;109:17472-7 pubmed publisher
    ..Thus, PI(3,5)P(2) and PI5P have major roles in multiple organs. Understanding the regulation of these lipids may provide insights into therapies for multiple diseases. ..
  8. Ikonomov O, Sbrissa D, Fligger J, Delvecchio K, Shisheva A. ArPIKfyve regulates Sac3 protein abundance and turnover: disruption of the mechanism by Sac3I41T mutation causing Charcot-Marie-Tooth 4J disorder. J Biol Chem. 2010;285:26760-4 pubmed publisher
    The mammalian phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P(2)) phosphatase Sac3 and ArPIKfyve, the associated regulator of the PtdIns3P-5 kinase PIKfyve, form a stable binary complex that associates with PIKfyve in a ternary ..
  9. Vaccari I, Dina G, Tronchère H, Kaufman E, Chicanne G, Cerri F, et al. Genetic interaction between MTMR2 and FIG4 phospholipid phosphatases involved in Charcot-Marie-Tooth neuropathies. PLoS Genet. 2011;7:e1002319 pubmed publisher
    ..Reduction of Fig4 by null heterozygosity and downregulation of PIKfyve both rescue Mtmr2-null myelin outfoldings in vivo and in vitro. ..

More Information

Publications20

  1. Ferguson C, Lenk G, Jones J, Grant A, Winters J, Dowling J, et al. Neuronal expression of Fig4 is both necessary and sufficient to prevent spongiform neurodegeneration. Hum Mol Genet. 2012;21:3525-34 pubmed publisher
    ..The data demonstrate that expression of Fig4 in neurons is necessary and sufficient to prevent spongiform degeneration. Therapy for patients with FIG4 deficiency will therefore require correction of the deficiency in neurons. ..
  2. Winters J, Ferguson C, Lenk G, Giger Mateeva V, Shrager P, Meisler M, et al. Congenital CNS hypomyelination in the Fig4 null mouse is rescued by neuronal expression of the PI(3,5)P(2) phosphatase Fig4. J Neurosci. 2011;31:17736-51 pubmed publisher
    The plt (pale tremor) mouse carries a null mutation in the Fig4(Sac3) gene that results in tremor, hypopigmentation, spongiform degeneration of the brain, and juvenile lethality...
  3. Bridges D, Ma J, Park S, Inoki K, Weisman L, Saltiel A. Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1. Mol Biol Cell. 2012;23:2955-62 pubmed publisher
    ..Furthermore, the mTORC1 component Raptor directly interacts with PI(3,5)P(2). Together these results suggest that PI(3,5)P(2) is an essential mTORC1 regulator that defines the localization of the complex. ..
  4. Lenk G, Frei C, Miller A, Wallen R, Mironova Y, Giger R, et al. Rescue of neurodegeneration in the Fig4 null mouse by a catalytically inactive FIG4 transgene. Hum Mol Genet. 2016;25:340-7 pubmed publisher
    ..The late onset phenotype of the NSE-Fig4(Cys486Ser) transgenic mice demonstrates that the phosphatase activity of FIG4 has an essential role in vivo. ..
  5. Khuda S, Yoshida M, Xing Y, Shimasaki T, Takeya M, Kuwahara K, et al. The Sac3 homologue shd1 is involved in mitotic progression in mammalian cells. J Biol Chem. 2004;279:46182-90 pubmed
    Saccharomyces Sac3 required for actin assembly was shown to be involved in DNA replication. Here, we studied the function of a mammalian homologue SHD1 in cell cycle progression...
  6. Reifler A, Lenk G, Li X, Groom L, Brooks S, Wilson D, et al. Murine Fig4 is dispensable for muscle development but required for muscle function. Skelet Muscle. 2013;3:21 pubmed publisher
    ..Overall, these data indicate that loss of Fig4 impairs skeletal muscle function but does not significantly affect its structural development. ..
  7. Zhang Y, McCartney A, Zolov S, Ferguson C, Meisler M, Sutton M, et al. Modulation of synaptic function by VAC14, a protein that regulates the phosphoinositides PI(3,5)P? and PI(5)P. EMBO J. 2012;31:3442-56 pubmed publisher
    ..Thus, VAC14, PI(3,5)P(2) and/or PI(5)P play a role in controlling postsynaptic function via regulation of endocytic cycling of AMPA receptors. ..
  8. Guo J, Ma Y, Yan Q, Wang L, Zeng Y, Wu J, et al. Fig4 expression in the rodent nervous system and its potential role in preventing abnormal lysosomal accumulation. J Neuropathol Exp Neurol. 2012;71:28-39 pubmed publisher
    ..We speculate that adequate levels of Fig4 may be required to prevent neurons and glia from excessive lysosomal accumulation after injury and in neurodegeneration. ..
  9. Ikonomov O, Sbrissa D, Ijuin T, Takenawa T, Shisheva A. Sac3 is an insulin-regulated phosphatidylinositol 3,5-bisphosphate phosphatase: gain in insulin responsiveness through Sac3 down-regulation in adipocytes. J Biol Chem. 2009;284:23961-71 pubmed publisher
    ..activator ArPIKfyve in 3T3L1 adipocytes suggests that dysfunction of the PtdIns(3,5)P(2)-specific phosphatase Sac3 may yield the opposite effect...
  10. Porrello E, Rivellini C, Dina G, Triolo D, Del Carro U, Ungaro D, et al. Jab1 regulates Schwann cell proliferation and axonal sorting through p27. J Exp Med. 2014;211:29-43 pubmed publisher
    ..Finally, Jab1 may constitute a key molecule in the pathogenesis of dysmyelinating neuropathies. ..
  11. Vaccari I, Carbone A, Previtali S, Mironova Y, Alberizzi V, Noseda R, et al. Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy. Hum Mol Genet. 2015;24:383-96 pubmed publisher
    ..Our data suggest that impaired endolysosomal trafficking in both motor neurons and Schwann cells contributes to CMT4J neuropathy. ..