TAM Signaling in the Nervous System

Overview

Journal Brain Plast

Publisher IOS Press

Date 2021 Oct 11

PMID 34631419

Citations 8

Authors

Tal Burstyn-Cohen

Arielle Hochberg

Affiliations

Soon will be listed here.

Abstract

Tyro3, Axl and Mertk are members of the family of tyrosine kinase receptors. TAMs are activated by two structurally homologous ligands and . TAM receptors and ligands are widely distributed and often co-expressed in the same cells allowing diverse functions across many systems including the , reproductive, vascular, and the developing as well as adult . This review will focus specifically on in the nervous system, highlighting the essential roles this pathway fulfills in maintaining cell survival and , cellular functions such as , immunity and tissue repair. Dysfunctional TAM signaling can cause complications in development, disruptions in homeostasis which can rouse autoimmunity, and . The development of therapeutics modulating TAM activities in the nervous system has great prospects, however, foremost we need a complete understanding of TAM signaling pathways.

Citing Articles

Therapeutic targeting of the functionally elusive TAM receptor family.

Miao Y, Rankin E, Giaccia A Nat Rev Drug Discov. 2023; 23(3):201-217.

PMID: 38092952 PMC: 11335090. DOI: 10.1038/s41573-023-00846-8.

TAM family kinases as therapeutic targets at the interface of cancer and immunity.

DeRyckere D, Huelse J, Earp H, Graham D Nat Rev Clin Oncol. 2023; 20(11):755-779.

PMID: 37667010 DOI: 10.1038/s41571-023-00813-7.

ARL6IP5 Ameliorates α-Synuclein Burden by Inducing Autophagy via Preventing Ubiquitination and Degradation of ATG12.

Siddique I, Kamble K, Gupta S, Solanki K, Bhola S, Ahsan N Int J Mol Sci. 2023; 24(13).

PMID: 37445677 PMC: 10341401. DOI: 10.3390/ijms241310499.

Pharmacological profiling identifies divergent chemosensitivities of differentiating and maturing iPSC-derived human cortical neuron populations.

Sharlow E, Llaneza D, Tewari B, Mingledorff G, Mendelson A, Sontheimer H FEBS J. 2023; 290(20):4950-4965.

PMID: 37428551 PMC: 10592385. DOI: 10.1111/febs.16901.

Gas6/AXL pathway: immunological landscape and therapeutic potential.

Zhai X, Pu D, Wang R, Zhang J, Lin Y, Wang Y Front Oncol. 2023; 13:1121130.

PMID: 37265798 PMC: 10231434. DOI: 10.3389/fonc.2023.1121130.

References

Sainaghi P, Bellan M, Lombino F, Alciato F, Carecchio M, Galimberti D . Growth Arrest Specific 6 Concentration is Increased in the Cerebrospinal Fluid of Patients with Alzheimer's Disease. J Alzheimers Dis. 2016; 55(1):59-65. DOI: 10.3233/JAD-160599. View

Yin J, Valin K, Dixon M, Leavenworth J . The Role of Microglia and Macrophages in CNS Homeostasis, Autoimmunity, and Cancer. J Immunol Res. 2018; 2017:5150678. PMC: 5749282. DOI: 10.1155/2017/5150678. View

Allen M, Xu M, Linseman D, Pawlowski J, Bokoch G, Heidenreich K . Adhesion-related kinase repression of gonadotropin-releasing hormone gene expression requires Rac activation of the extracellular signal-regulated kinase pathway. J Biol Chem. 2002; 277(41):38133-40. DOI: 10.1074/jbc.M200826200. View

Shafit-Zagardo B, Gruber R, DuBois J . The role of TAM family receptors and ligands in the nervous system: From development to pathobiology. Pharmacol Ther. 2018; 188:97-117. PMC: 6067981. DOI: 10.1016/j.pharmthera.2018.03.002. View

Akkermann R, Aprico A, Perera A, Bujalka H, Cole A, Xiao J . The TAM receptor Tyro3 regulates myelination in the central nervous system. Glia. 2017; 65(4):581-591. DOI: 10.1002/glia.23113. View

Kotter M, Li W, Zhao C, Franklin R . Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J Neurosci. 2006; 26(1):328-32. PMC: 6674302. DOI: 10.1523/JNEUROSCI.2615-05.2006. View

Axelrod H, Pienta K . Axl as a mediator of cellular growth and survival. Oncotarget. 2014; 5(19):8818-52. PMC: 4253401. DOI: 10.18632/oncotarget.2422. View

Lu Q, Lemke G . Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science. 2001; 293(5528):306-11. DOI: 10.1126/science.1061663. View

Zheng Y, Zhang L, Lu Q, Wang X, Yu F, Wang X . NGF-induced Tyro3 and Axl function as survival factors for differentiating PC12 cells. Biochem Biophys Res Commun. 2008; 378(3):371-5. DOI: 10.1016/j.bbrc.2008.11.049. View

10.

Binder M, Cate H, Prieto A, Kemper D, Butzkueven H, Gresle M . Gas6 deficiency increases oligodendrocyte loss and microglial activation in response to cuprizone-induced demyelination. J Neurosci. 2008; 28(20):5195-206. PMC: 3844801. DOI: 10.1523/JNEUROSCI.1180-08.2008. View

11.

Tsiperson V, Li X, Schwartz G, Raine C, Shafit-Zagardo B . GAS6 enhances repair following cuprizone-induced demyelination. PLoS One. 2011; 5(12):e15748. PMC: 3009745. DOI: 10.1371/journal.pone.0015748. View

12.

Brosius Lutz A, Chung W, Sloan S, Carson G, Zhou L, Lovelett E . Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury. Proc Natl Acad Sci U S A. 2017; 114(38):E8072-E8080. PMC: 5617301. DOI: 10.1073/pnas.1710566114. View

13.

Lew E, Oh J, Burrola P, Lax I, Zagorska A, Traves P . Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. Elife. 2014; 3. PMC: 4206827. DOI: 10.7554/eLife.03385. View

14.

Kister I, Bacon T, Chamot E, Salter A, Cutter G, Kalina J . Natural history of multiple sclerosis symptoms. Int J MS Care. 2014; 15(3):146-58. PMC: 3883021. DOI: 10.7224/1537-2073.2012-053. View

15.

Linger R, Keating A, Earp H, Graham D . TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res. 2008; 100:35-83. PMC: 3133732. DOI: 10.1016/S0065-230X(08)00002-X. View

16.

Kim D, Yu J, Mui R, Niibori R, Taufique H, Aslam R . The tyrosine kinase receptor Tyro3 enhances lifespan and neuropeptide Y (Npy) neuron survival in the mouse anorexia () mutation. Dis Model Mech. 2017; 10(5):581-595. PMC: 5451163. DOI: 10.1242/dmm.027433. View

17.

Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J . Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018; 9(6):7204-7218. PMC: 5805548. DOI: 10.18632/oncotarget.23208. View

18.

Li Y, Li Y, Li X, Zhang S, Zhao J, Zhu X . Head Injury as a Risk Factor for Dementia and Alzheimer's Disease: A Systematic Review and Meta-Analysis of 32 Observational Studies. PLoS One. 2017; 12(1):e0169650. PMC: 5221805. DOI: 10.1371/journal.pone.0169650. View

19.

Binder M, Kilpatrick T . TAM receptor signalling and demyelination. Neurosignals. 2009; 17(4):277-87. DOI: 10.1159/000231894. View

20.

Zhang M, Qian C, Zheng Z, Qian F, Wang Y, Thu P . Jujuboside A promotes Aβ clearance and ameliorates cognitive deficiency in Alzheimer's disease through activating Axl/HSP90/PPARγ pathway. Theranostics. 2018; 8(15):4262-4278. PMC: 6096387. DOI: 10.7150/thno.26164. View