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GPSM2  -  G-protein signaling modulator 2

Homo sapiens

Synonyms: CMCS, DFNB82, G-protein-signaling modulator 2, LGN, Mosaic protein LGN, ...
 
 
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Disease relevance of GPSM2

  • The prototype PEV that was tested also revealed less marked hyperventilation with small decreases (down to -10% of the VE at higher Pinsp values) [1].
  • In humans with albinism, a large percentage of the ganglion cell axons from the temporal retina decussate abnormally in the chiasm and synapse in the contralateral LGN [2].
  • Neuroanatomical evidence suggests that poor readers may have abnormal lateral (LGN) and medial (MGN) geniculate nuclei responsible for temporal processing in visual and auditory domains respectively (Livingstone & Galaburda, 1993) [3].
  • Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN [4].
  • Endocrinologic causes of peripheral neuropathy. Pins and needles in a stocking-and-glove pattern and other symptoms [5].
 

Psychiatry related information on GPSM2

  • Quantitative modeling of the result implied a weak role for magnocellular input, suggests that human stereopsis is more strongly influenced by parvocellular input through the LGN [6].
 

High impact information on GPSM2

  • During mitosis, LGN recruits NuMA to the cell cortex, while cortical association of LGN itself requires the C-terminal Galpha binding domain [7].
  • Overexpression of Galphai or YFP-LGN causes a pronounced oscillation of metaphase spindles, and NuMA binding to LGN is required for these spindle movements [7].
  • A mammalian Pins, called LGN, binds Galphai and also interacts through an N-terminal domain with the microtubule binding protein NuMA [7].
  • I have compared the numbers of neurons in the visual thalamus (lateral geniculate nucleus; LGN) and area V1 across primate species [8].
  • Our results provide evidence for a functional role of the LGN in binocular rivalry and suggest that the LGN, traditionally viewed as the gateway to the visual cortex, may be an early gatekeeper of visual awareness [9].
 

Biological context of GPSM2

 

Anatomical context of GPSM2

  • We find that in WISH, PC12, and NRK but not COS cells, LGN is largely directed to the cell cortex during mitosis [11].
  • In Drosophila, Pins localizes to the lateral cortex of polarized epithelial cells and to the apical cortex of neuroblasts where it plays important roles in their asymmetric division [11].
  • Using overexpression studies in different cell line systems, we demonstrate here that, like Drosophila Pins, LGN can exhibit enriched localization at the cell cortex, depending on the cell cycle and the culture system used [11].
  • The results also show that the cortical localization of LGN is dependent on microfilaments and that interfering with LGN function in cultured cell lines causes early disruption to cell cycle progression [11].
  • The progenitor cell marker nestin also localizes asymmetrically in colcemid-treated hNPCs and colocalizes with LGN [12].
 

Associations of GPSM2 with chemical compounds

  • A portion of the magnocellular pathway was permanently and selectively interrupted by ibotenic acid injections in the LGN of macaque monkeys [13].
  • Striate layers 4Ca and 4B-appeared color-insensitive in a wide variety of DG tests; this supports the idea of a color-insensitive stream running from the magnocellular LGN layers through striate layers 4Ca and 4B to extrastriate areas MT and V3 [14].
  • We first used tritiated thymidine labeling to trace relative changes in the numbers of identified cohorts of cells in the subplate, layer VI, and the LGN [15].
  • In addition, RGS12, RGS14 and LOCO are shown to contain single "LGN motifs" that are guanine nucleotide exchange factors specific for the alpha-subunit of G proteins [16].
  • At the high IPS level, VT at FICO2 of 0 was significantly above the value at lower Pinsp and did not increase with CO2 unless FICO2 was elevated to > 0.03 [17].
 

Physical interactions of GPSM2

  • The C-terminal tail of Lgl2 bound to LGN with a K(d) value of about 56 nm [18].
 

Other interactions of GPSM2

  • Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division [18].
  • Asymmetric localization of LGN but not AGS3, two homologs of Drosophila pins, in dividing human neural progenitor cells [12].
  • Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins [7].
  • We have also observed that LGN, a Galphai-interacting protein with seven TPR motifs, binds Ha-Ras [19].
  • To investigate ventilatory CO2 sensitivity during inspiratory pressure support (IPS), we administered inspiratory CO2 [fractional concn (FICO2) 0.01, 0.03, or 0.05] in eight normal subjects without (CTRL) or with (Pinsp) positive inspiratory airway pressure (5 or 10 cmH2O) [17].
 

Analytical, diagnostic and therapeutic context of GPSM2

  • Subcellular localization of LGN during mitosis: evidence for its cortical localization in mitotic cell culture systems and its requirement for normal cell cycle progression [11].
  • Using a FRET biosensor, we find that LGN behaves as a conformational switch: in its closed state, the N and C termini interact, but NuMA or Galphai can disrupt this association, allowing LGN to interact simultaneously with both proteins, resulting in their cortical localization [7].
  • In primary neuronal cultures as well as in dividing cultures of PC12 cells, immunocytochemistry indicated distinct subcellular locations of AGS3 and LGN [20].
  • RT-PCR analysis of human tissues showed that the mRNA of LGN was ubiquitously expressed [21].
  • Here we used fMRI to measure neural activity in the human LGN while subjects viewed contrast-modulated gratings presented dichoptically [9].

References

  1. Accuracy of delivered versus preset minute ventilation of portable emergency ventilators. Heinrichs, W., Mertzlufft, F., Dick, W. Crit. Care Med. (1989) [Pubmed]
  2. New method for detecting misrouted retinofugal fibers in humans with albinism by magnetoencephalography. Ohde, H., Shinoda, K., Nishiyama, T., Kado, H., Haruta, Y., Mashima, Y., Oguchi, Y. Vision Res. (2004) [Pubmed]
  3. Cross-modality temporal processing deficits in developmental phonological dyslexics. Cestnick, L. Brain and cognition. (2001) [Pubmed]
  4. Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Dacey, D.M., Liao, H.W., Peterson, B.B., Robinson, F.R., Smith, V.C., Pokorny, J., Yau, K.W., Gamlin, P.D. Nature (2005) [Pubmed]
  5. Endocrinologic causes of peripheral neuropathy. Pins and needles in a stocking-and-glove pattern and other symptoms. Perkins, A.T., Morgenlander, J.C. Postgraduate medicine. (1997) [Pubmed]
  6. Relative contributions of sustained and transient pathways to human stereoprocessing. Kontsevich, L.L., Tyler, C.W. Vision Res. (2000) [Pubmed]
  7. Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Du, Q., Macara, I.G. Cell (2004) [Pubmed]
  8. An evolutionary scaling law for the primate visual system and its basis in cortical function. Stevens, C.F. Nature (2001) [Pubmed]
  9. Neural correlates of binocular rivalry in the human lateral geniculate nucleus. Wunderlich, K., Schneider, K.A., Kastner, S. Nat. Neurosci. (2005) [Pubmed]
  10. A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization. Du, Q., Stukenberg, P.T., Macara, I.G. Nat. Cell Biol. (2001) [Pubmed]
  11. Subcellular localization of LGN during mitosis: evidence for its cortical localization in mitotic cell culture systems and its requirement for normal cell cycle progression. Kaushik, R., Yu, F., Chia, W., Yang, X., Bahri, S. Mol. Biol. Cell (2003) [Pubmed]
  12. Asymmetric localization of LGN but not AGS3, two homologs of Drosophila pins, in dividing human neural progenitor cells. Fuja, T.J., Schwartz, P.H., Darcy, D., Bryant, P.J. J. Neurosci. Res. (2004) [Pubmed]
  13. Does primate motion perception depend on the magnocellular pathway? Merigan, W.H., Byrne, C.E., Maunsell, J.H. J. Neurosci. (1991) [Pubmed]
  14. Functional anatomy of macaque striate cortex. III. Color. Tootell, R.B., Silverman, M.S., Hamilton, S.L., De Valois, R.L., Switkes, E. J. Neurosci. (1988) [Pubmed]
  15. Dual fate of subplate neurons in a rodent. Woo, T.U., Beale, J.M., Finlay, B.L. Cereb. Cortex (1991) [Pubmed]
  16. Raf-like Ras/Rap-binding domains in RGS12- and still-life-like signalling proteins. Ponting, C.P. J. Mol. Med. (1999) [Pubmed]
  17. Respiratory response to inhaled CO2 during positive inspiratory pressure in humans. Scheid, P., Lofaso, F., Isabey, D., Harf, A. J. Appl. Physiol. (1994) [Pubmed]
  18. Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division. Yasumi, M., Sakisaka, T., Hoshino, T., Kimura, T., Sakamoto, Y., Yamanaka, T., Ohno, S., Takai, Y. J. Biol. Chem. (2005) [Pubmed]
  19. Identification of tetratricopeptide repeat 1 as an adaptor protein that interacts with heterotrimeric G proteins and the small GTPase Ras. Marty, C., Browning, D.D., Ye, R.D. Mol. Cell. Biol. (2003) [Pubmed]
  20. Expression analysis and subcellular distribution of the two G-protein regulators AGS3 and LGN indicate distinct functionality. Localization of LGN to the midbody during cytokinesis. Blumer, J.B., Chandler, L.J., Lanier, S.M. J. Biol. Chem. (2002) [Pubmed]
  21. Identification and cDNA cloning of a novel human mosaic protein, LGN, based on interaction with G alpha i2. Mochizuki, N., Cho, G., Wen, B., Insel, P.A. Gene (1996) [Pubmed]
 
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