Skip to main content
Log in

Medical molecular morphology with imaging mass spectrometry

  • Review
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

Imaging mass spectrometry (IMS) is a two-dimensional mass spectrometry to visualize the spatial distribution of biomolecules that does not need either separation or purification of target molecules and enables us to monitor not only the identification of unknown molecules but also the localization of numerous molecules simultaneously. Among the ionization techniques, matrix-assisted laser desorption/ionization (MALDI) is one of those most generally used for IMS, which allows the analysis of numerous biomolecules ranging over wide molecular weights. At present, targets of IMS research have expanded to the imaging of small endogenous metabolites such as lipids, exogenous drug pharmacokinetics, exploring new disease markers, and other new scientific fields.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y, Yoshida T (1988) Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2:151–153

    Article  CAS  Google Scholar 

  2. Takats Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473

    Article  PubMed  CAS  Google Scholar 

  3. Benninghoven A (1973) Surface investigation of solids by the statical method of secondary ion mass spectroscopy (SIMS). Surface Sci 35:427–457

    Article  CAS  Google Scholar 

  4. Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7:493–496

    Article  PubMed  CAS  Google Scholar 

  5. Hosokawa N, Sugiura Y, Setou M (2008) Spectrum normalization method using an external standard in mass spectrometric imaging. J Mass Spectrom Soc Jpn 56:77–81

    CAS  Google Scholar 

  6. Shimma S, Furuta M, Ichimura K, Yoshida Y, Setou M (2006) A novel approach to in situ proteome analysis using chemical inkjet printing technology and MALDI-QIT-TOF tandem mass spectrometer. J Mass Spectrom Soc Jpn 54:133–140

    CAS  Google Scholar 

  7. Sugiura Y, Shimma S, Setou M (2006) Thin sectioning improves the peak intensity and signal-to-noise ratio in direct tissue mass spectrometry. J Mass Spectrom Soc Jpn 54:4

    Google Scholar 

  8. Moritake S, Taira S, Ichiyanagi Y, Morone N, Song S-Y, Hatanaka T, Yusawa S, Setou M (2007) Functionalized nano-magnetic particles for an in vivo delivery system. J Nanosci Nanotechnol 7: 937–944

    Article  PubMed  CAS  Google Scholar 

  9. Moritake S, Taira S, Sugiura Y, Setou M, Ichiyanagi Y (2009) Magnetic nanoparticle-based mass spectrometry for the detection of biomolecules in cultured cells. J Nanosci Nanotechnol 9:169–176

    Article  PubMed  CAS  Google Scholar 

  10. Taira S, Sugiura Y, Moritake S, Shimma S, Ichiyanagi Y, Setou M (2008) Nanoparticle-assisted laser desorption/ionization based mass imaging with cellular resolution. Anal Chem 80:4761–4766

    Article  PubMed  CAS  Google Scholar 

  11. Ageta H, Asai S, Sugiura Y, Goto-Inoue N, Zaima N, Setou M (2009) Layer-specific sulfatide localization in rat hippocampus middle molecular layer is revealed by nanoparticle-assisted laser desorption/ionization imaging mass spectrometry. Med Mol Morphol 42:16–23

    Article  PubMed  CAS  Google Scholar 

  12. Luxembourg SL, Mize TH, McDonnell LA, Heeren RM (2004) High-spatial resolution mass spectrometric imaging of peptide and protein distributions on a surface. Anal Chem 76:5339–5344

    Article  PubMed  CAS  Google Scholar 

  13. Yao I, Sugiura Y, Matsumoto M, Setou M (2008) In situ proteomics with imaging mass spectrometry and principal component analysis in the Scrapper-knockout mouse brain. Proteomics 8: 3692–3701

    Article  PubMed  CAS  Google Scholar 

  14. Hatanaka T, Hatanaka Y, Tsuchida J, Ganapathy V, Setou M (2006) Amino acid transporter ATA2 is stored at the trans-Golgi network and released by insulin stimulus in adipocytes. J Biol Chem 281:39273–39284

    Article  PubMed  CAS  Google Scholar 

  15. Konishi Y, Setou M (2009) Tubulin tyrosination navigates the kinesin-1 motor domain to axons. Nat Neurosci 12:559–567

    Article  PubMed  CAS  Google Scholar 

  16. Yang H, Takagi H, Konishi Y, Ageta H, Ikegami K, Yao I, Sato S, Hatanaka K, Inokuchi K, Seog DH, Setou M (2008) Transmembrane and ubiquitin-like domain-containing protein 1 (Tmub1/HOPS) facilitates surface expression of GluR2-containing AMPA receptors. PLoS ONE 3:e2809

    Article  PubMed  CAS  Google Scholar 

  17. Fukuda Y, Kawano Y, Tanikawa Y, Oba M, Koyama M, Takagi H, Matsumoto M, Nagayama K, Setou M (2006) In vivo imaging of the dendritic arbors of layer V pyramidal cells in the cerebral cortex using a laser scanning microscope with a stick-type objective lens. Neurosci Lett 400:53–57

    Article  PubMed  CAS  Google Scholar 

  18. Ikegami K, Heier RL, Taruishi M, Takagi H, Mukai M, Shimma S, Taira S, Hatanaka K, Morone N, Yao I, Campbell PK, Yuasa S, Janke C, Macgregor GR, Setou M (2007) Loss of alpha-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function. Proc Natl Acad Sci U S A 104:3213–3218

    Article  PubMed  CAS  Google Scholar 

  19. Yao I, Takagi H, Ageta H, Kahyo T, Sato S, Hatanaka K, Fukuda Y, Chiba T, Morone N, Yuasa S, Inokuchi K, Ohtsuka T, Macgregor GR, Tanaka K, Setou M (2007) SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell 130:943–957

    Article  PubMed  CAS  Google Scholar 

  20. Hatanaka T, Hatanaka Y, Setou M (2006) Regulation of amino acid transporter ATA2 by ubiquitin ligase Nedd4-2. J Biol Chem 281:35922–35930

    Article  PubMed  CAS  Google Scholar 

  21. Ikegami K, Mukai M, Tsuchida J, Heier RL, Macgregor GR, Setou M (2006) TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites. J Biol Chem 281:30707–30716

    Article  PubMed  CAS  Google Scholar 

  22. Asai S, Takamura K, Suzuki H, Setou M (2008) Single-cell imaging of c-fos expression in rat primary hippocampal cells using a luminescence microscope. Neurosci Lett 434:289–292

    Article  PubMed  CAS  Google Scholar 

  23. Setou M, Radostin D, Atsuzawa K, Yao I, Fukuda Y, Usuda N, Nagayama K (2006) Mammalian cell nano structures visualized by cryo Hilbert differential contrast transmission electron microscopy. Med Mol Morphol 39:176–180

    Article  PubMed  Google Scholar 

  24. Goto-Inoue N, Hayasaka T, Sugiura Y, Taki T, Li YT, Matsumoto M, Setou M (2008) High-sensitivity analysis of glycosphingolipids by matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight imaging mass spectrometry on transfer membranes. J Chromatogr B Anal Technol Biomed Life Sci 870:74–83

    Article  CAS  Google Scholar 

  25. Hayasaka T, Goto-Inoue N, Sugiura Y, Zaima N, Nakanishi H, Ohishi K, Nakanishi S, Naito T, Taguchi R, Setou M (2008) Matrixassisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)-based imaging mass spectrometry reveals a layered distribution of phospholipid molecular species in the mouse retina. Rapid Commun Mass Spectrom 22:3415–3426

    Article  PubMed  CAS  Google Scholar 

  26. Shimma S, Setou M (2007) Mass microscopy to reveal distinct localization of Heme B (m/z 616) in colon cancer liver metastasis. J Mass Spectrom Soc Jpn 55:230–238

    Google Scholar 

  27. Shimma S, Sugiura Y, Hayasaka T, Hoshikawa Y, Noda T, Setou M (2007) MALDI-based imaging mass spectrometry revealed abnormal distribution of phospholipids in colon cancer liver metastasis. J Chromatogr B Anal Technol Biomed Life Sci 855:98–103

    Article  CAS  Google Scholar 

  28. Sugiura Y, Konishi Y, Zaima N, Kajihara S, Nakanishi H, Taguchi R, Setou M (2009) Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry. J Lipid Res (in press)

  29. Sugiura Y, Shimma S, Konishi Y, Yamada MK, Setou M (2008) Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglioside molecular species in the mouse hippocampus. PLoS ONE 3:e3232

    Article  PubMed  CAS  Google Scholar 

  30. Ikegami K, Horigome D, Mukai M, Livnat I, MacGregor GR, Setou M (2008) TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1. FEBS Lett 582:1129–1134

    Article  PubMed  CAS  Google Scholar 

  31. Setou M, Nakagawa T, Seog DH, Hirokawa N (2000) Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288:1796–1802

    Article  PubMed  CAS  Google Scholar 

  32. Setou M, Seog DH, Tanaka Y, Kanai Y, Takei Y, Kawagishi M, Hirokawa N (2002) Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Nature 417:83–87

    Article  PubMed  CAS  Google Scholar 

  33. Hatanaka K, Ikegami K, Takagi H, Setou M (2006) Hypo-osmotic shock induces nuclear export and proteasome-dependent decrease of UBL5. Biochem Biophys Res Commun 350:610–615

    Article  PubMed  CAS  Google Scholar 

  34. Zaima N, Matsuyama Y, Setou M (2009) Principal component analysis of direct matrix-assisted laser desorption/ionization mass spectrometric data related to metabolites of fatty liver. J Oleo Sci 58:267–273

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mitsutoshi Setou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kimura, Y., Tsutsumi, K., Sugiura, Y. et al. Medical molecular morphology with imaging mass spectrometry. Med Mol Morphol 42, 133–137 (2009). https://doi.org/10.1007/s00795-009-0458-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-009-0458-7

Key words

Navigation