Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Kalirin

  • Xin-Ming Ma
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101733

Synonyms

Historical Background

Kalirin ( Kal) was discovered as an interactor of the cytosolic domain of peptidylglycine α-amidating monooxygenase (PAM), a secretory granule membrane protein in 1996 (Alam et al. 1996). Kalirin is a Rho guanine nucleotide exchange factor (Rho GEF) that regulates critical processes necessary for the formation of dendritic spines, synaptic plasticity, and neurite outgrowth through activating small Rho GTPase including Rac1, RhoG, and RhoA. Rho GTPases play essential roles in regulating dendritic spine formation and synapse plasticity through regulating the actin cytoskeleton by functioning as molecular switches, exchanging between an active GTP-bound state and an inactive GDP-bound state (Miller et al. 2013). Multiple kalirin isoforms are generated...
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Notes

Acknowledgment

Thanks to Dr. Mains for his reading the manuscript.

References

  1. Alam MR, Caldwell BD, Johnson RC, Darlington DN, Mains RE, Eipper BA. Novel proteins that interact with the COOH-terminal cytosolic routing determinants of an integral membrane peptide-processing enzyme. J Biol Chem. 1996;271(45):28636–40.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Cahill ME, Xie Z, Day M, Barbolina MV, Miller CA, Weiss C, et al. Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes. Proc Natl Acad Sci USA. 2009;106(31):13058–63.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Johnson RC, Penzes P, Eipper BA, Mains RE. Isoforms of kalirin, a neuronal Dbl family member, generated through use of different 5′- and 3′-ends along with an internal translational initiation site. J Biol Chem. 2000;275(25):19324–33.CrossRefPubMedGoogle Scholar
  4. Kiraly DD, Ma XM, Mazzone CM, Xin X, Mains RE, Eipper BA. Behavioral and morphological responses to cocaine require kalirin7. Biol Psychiatry. 2010;68(3):249–55.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Kiraly DD, Stone KL, Colangelo CM, Abbott T, Wang Y, Mains RE, et al. Identification of kalirin-7 as a potential post-synaptic density signaling hub. J Proteome Res. 2011;10(6):2828–41.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Ma XM. Kalirin-7 is a key player in the formation of excitatory synapses in hippocampal neurons. ScientificWorldJournal. 2010;10:1655–66.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Ma XM, Johnson RC, Mains RE, Eipper BA. Expression of kalirin, a neuronal GDP/GTP exchange factor of the trio family, in the central nervous system of the adult rat. J Comp Neurol. 2001;429(3):388–402.CrossRefPubMedGoogle Scholar
  8. Ma XM, Huang J, Wang Y, Eipper BA, Mains RE. Kalirin, a multifunctional Rho guanine nucleotide exchange factor, is necessary for maintenance of hippocampal pyramidal neuron dendrites and dendritic spines. J Neurosci. 2003;23(33):10593–603.CrossRefPubMedGoogle Scholar
  9. Ma XM, Kiraly DD, Gaier ED, Wang Y, Kim EJ, Levine ES, et al. Kalirin-7 is required for synaptic structure and function. J Neurosci. 2008a;28(47):12368–82.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Ma XM, Wang Y, Ferraro F, Mains RE, Eipper BA. Kalirin-7 is an essential component of both shaft and spine excitatory synapses in hippocampal interneurons. J Neurosci. 2008b;28(3):711–24.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Ma XM, Huang JP, Xin X, Yan Y, Mains RE, Eipper BA. A role for kalirin in the response of rat medium spiny neurons to cocaine. Mol Pharmacol. 2012;82(4):738–45.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Ma XM, Miller MB, Vishwanatha KS, Gross MJ, Wang Y, Abbott T, et al. Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl. Mol Biol Cell. 2014;25(9):1458–71.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Mandela P, Ma XM. Kalirin, a key player in synapse formation, is implicated in human diseases. Neural Plast. 2012;2012:728161.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Mandela P, Yankova M, Conti LH, Ma XM, Grady J, Eipper BA, et al. Kalrn plays key roles within and outside of the nervous system. BMC Neurosci. 2012;13:136.PubMedPubMedCentralCrossRefGoogle Scholar
  15. McPherson CE, Eipper BA, Mains RE. Kalirin expression is regulated by multiple promoters. J Mol Neurosci. 2004;22(1–2):51–62.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Miller MB, Yan Y, Eipper BA, Mains RE. Neuronal Rho GEFs in synaptic physiology and behavior. Neuroscientist. 2013;19(3):255–73.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Penzes P, Johnson RC, Sattler R, Zhang X, Huganir RL, Kambampati V, et al. The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron. 2001;29(1):229–42.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Penzes P, Beeser A, Chernoff J, Schiller MR, Eipper BA, Mains RE, et al. Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron. 2003;37(2):263–74.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Penzes P, Buonanno A, Passafaro M, Sala C, Sweet RA. Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders. J Neurochem. 2013;126(2):165–82.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Xu C, Ma XM, Chen HB, Zhou MH, Qiao H, An SC. Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7. Neuropharmacology. 2016;109:7–17.CrossRefPubMedGoogle Scholar
  21. Yan Y, Eipper BA, Mains RE. Kalirin-9 and Kalirin-12 Play Essential Roles in Dendritic Outgrowth and Branching. Cereb Cortex. 2015;25(10):3487–501.CrossRefPubMedGoogle Scholar
  22. Yan Y, Eipper BA, Mains RE. Kalirin is required for BDNF-TrkB stimulated neurite outgrowth and branching. Neuropharmacology. 2016;107:227–38.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life ScienceShaanxi Normal UniversityXianChina
  2. 2.Department of NeuroscienceUniversity of Connecticut Health CenterFarmingtonUSA