Skip to main content
Log in

Morphological characterization of Class III phosphoinositide 3-kinase during mouse brain development

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

The mammalian Class III phosphoinositide 3-kinase (PIK3C3, also known as mammalian vacuolar protein sorting 34 homologue, Vps34) is a regulator of vesicular trafficking, autophagy, and nutrient sensing. In this study, we generated a specific antibody against PIK3C3, and carried out expression and morphological analyses of PIK3C3 during mouse brain development. In Western blotting, PIK3C3 was detected throughout the developmental process with higher expression in the early embryonic stage. In immunohistochemical analyses with embryonic day 16 mouse brain, PIK3C3 was detected strongly in the axon of cortical neurons. While PIK3C3 was distributed at the soma, nucleus, axon, and dendrites in primary cultured mouse hippocampal neurons at 3 days in vitro (div), it was also found in a punctate distribution with partial colocalization with synaptic marker, synaptophysin, at 21 div. The obtained results indicate that PIK3C3 is expressed and may have a physiological role in central nervous system during corticogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Fruman DA, Meyers RE, Cantley LC (1998) Phosphoinositide kinases. Annu Rev Biochem 67:481–507

    Article  CAS  PubMed  Google Scholar 

  2. Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, Woscholski R, Parker PJ, Waterfield MD (2001) Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem 70:535–602

    Article  CAS  PubMed  Google Scholar 

  3. Backer JM (2008) The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem J 410:1–17

    Article  CAS  PubMed  Google Scholar 

  4. Herman PK, Emr SD (1990) Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae. Mol Cell Biol 10:6742–6754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schu PV, Takegawa K, Fry MJ, Stack JH, Waterfield MD, Emr SD (1993) Phosphatidylinositol 3-kinase encoded by yeast VPS 34 gene essential for protein sorting. Science 260:88–91

    Article  CAS  PubMed  Google Scholar 

  6. Siddhanta U, McIlroy J, Shah A, Zhang Y, Backer JM (1998) Distinct roles for the p110alpha and hVPS34 phosphatidylinositol 3′-kinases in vesicular trafficking, regulation of the actin cytoskeleton, and mitogenesis. J Cell Biol 143:1647–1659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Christoforidis S, McBride HM, Burgoyne RD, Zerial M (1999) The Rab5 effector EEA1 is a core component of endosome docking. Nature 397:621–625

    Article  CAS  PubMed  Google Scholar 

  8. Nielsen E, Severin F, Backer JM, Hyman AA, Zerial M (1999) Rab5 regulates motility of early endosomes on microtubules. Nat Cell Biol 1:376–382

    Article  CAS  PubMed  Google Scholar 

  9. Futter CE, Collinson LM, Backer JM, Hopkins CR (2001) Human VPS34 is required for internal vesicle formation within multivesicular endosomes. J Cell Biol 155:1251–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fratti RA, Backer JM, Gruenberg J, Corvera S, Deretic V (2001) Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J Cell Biol 154:631–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vieira OV, Botelho RJ, Rameh L, Brachmann SM, Matsuo T, Davidson HW, Schreiber A, Backer JM, Cantley LC, Grinstein S (2001) Distinct roles of class I and class III phosphatidylinositol 3-kinases in phagosome formation and maturation. J Cell Biol 155:19–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Windmiller DA, Backer JM (2003) Distinct phosphoinositide 3-kinases mediate mast cell degranulation in response to G-protein-coupled versus FcεRI receptors. J Biol Chem 278:11874–11878

    Article  CAS  PubMed  Google Scholar 

  13. Waite K, Eickholt BJ (2010) The neurodevelopmental implications of PI3K signaling. Curr Top Microbiol Immunol 346:245–265

    CAS  PubMed  Google Scholar 

  14. Zhou X, Takatoh J, Wang F (2011) The mammalian class 3 PI3K (PIK3C3) is required for early embryogenesis and cell proliferation. PLoS ONE 6:e16358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang L, Budolfson K, Wang F (2011) Pik3c3 deletion in pyramidal neurons results in loss of synapses, extensive gliosis and progressive neurodegeneration. Neuroscience 172:427–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hanai N, Nagata K, Kawajiri A, Shiromizu T, Saitoh N, Hasegawa Y, Murakami S, Inagaki M (2004) Biochemical and cell biological characterization of a mammalian septin, Sept11. FEBS Lett 568:83–88

    Article  CAS  PubMed  Google Scholar 

  17. Sudo K, Ito H, Iwamoto I, Morishita R, Asano T, Nagata K (2006) Identification of a cell polarity-related protein, Lin-7B, as a binding partner for a Rho effector, Rhotekin, and their possible interaction in neurons. Neurosci Res 56:347–355

    Article  CAS  PubMed  Google Scholar 

  18. Nagata K, Ito H, Iwamoto I, Morishita R, Asano T (2009) Interaction of a multi-domain adaptor protein, vinexin, with a Rho-effector, Rhotekin. Med Mol Morphol 42:9–15

    Article  CAS  PubMed  Google Scholar 

  19. Ito H, Morishita R, Shinoda T, Iwamoto I, Sudo K, Okamoto K, Nagata K (2010) Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Mol Psychiatry 15:976–986

    Article  CAS  PubMed  Google Scholar 

  20. Murase K, Ito H, Kanoh H, Sudo K, Iwamoto I, Morishita R, Soubeyran P, Seishima M, Nagata K (2012) Cell biological characterization of a multi-domain adaptor protein, ArgBP2, in epithelial NMuMG cells, and identification of a novel short isoform. Med Mol Morphol 45:22–28

    Article  CAS  PubMed  Google Scholar 

  21. Inaguma Y, Ito H, Hara A, Iwamoto I, Matsumoto A, Yamagata T, Tabata H, Nagata K (2015) Morphological characterization of mammalian Timeless in the mouse brain development. Neurosci Res 92:21–28

    Article  PubMed  Google Scholar 

  22. Wolfer DP, Henehan-Beatty A, Stoeckli ET, Sonderegger P, Lipp HP (1994) Distribution of TAG-1/axonin-1 in fibre tracts and migratory streams of the developing mouse nervous system. J Comp Neurol 345:1–32

    Article  CAS  PubMed  Google Scholar 

  23. Wurmser AE, Gary JD, Emr SD (1999) Phosphoinositide 3-kinases and their FYVE domain-containing effectors as regulators of vacuolar/lysosomal membrane trafficking pathways. J Biol Chem 274:9129–9132

    Article  CAS  PubMed  Google Scholar 

  24. Lee KM, Hwang SK, Lee JA (2013) Neuronal Autophagy and neurodevelopmental disorders. Exp Neurobiol 22:133–142

    Article  PubMed  PubMed Central  Google Scholar 

  25. Liang XH, Yu J, Brown K, Levine B (2001) Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function. Cancer Res 61:3443–3449

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from Ministry of Education, Science, Technology, Sports, and Culture of Japan, a grant-in-aid of Health Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare, Japan, a grant-in-aid of the 24th General Assembly of the Japanese Association of Medical Science and Takeda Science Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Koh-ichi Nagata.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inaguma, Y., Ito, H., Iwamoto, I. et al. Morphological characterization of Class III phosphoinositide 3-kinase during mouse brain development. Med Mol Morphol 49, 28–33 (2016). https://doi.org/10.1007/s00795-015-0116-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-015-0116-1

Keywords

Navigation