Brain Meets Pancreas: Netrin, an Axon Guidance Molecule, Controls Epithelial Cell Migration

Overview

Journal Trends Cell Biol

Specialty Cell Biology

Date 2004 May 12

PMID 15134068

Citations 16

Authors

Matthias Hebrok

Louis F Reichardt

Affiliations

Soon will be listed here.

Abstract

A recent publication shows that two integrins, alpha6beta4 and alpha3beta1, interact with netrin-1, a protein best known for its role in axon guidance. Consistent with a role in pancreatic development in vivo, netrin is expressed together with these integrins in fetal pancreatic epithelium. The paper presents strong evidence that pancreatic epithelial cells adhere, spread and migrate on netrin-coated substrata through alpha6beta4. Data also indicate that alpha3beta1 mediates HGF-stimulated cell migration on netrin-coated substrata. These results indicate that netrins might have much broader functions than previously suspected.

Citing Articles

Brain phosphoproteomic analysis identifies diabetes-related substrates in Alzheimer's disease pathology in older adults.

Capuano A, Sarsani V, Tasaki S, Mehta R, Li J, Ahima R Alzheimers Dement. 2024; 21(2):e14460.

PMID: 39732516 PMC: 11848201. DOI: 10.1002/alz.14460.

On the use of QDE-SVM for gene feature selection and cell type classification from scRNA-seq data.

Ng G, Tan S, Ong C PLoS One. 2023; 18(10):e0292961.

PMID: 37856458 PMC: 10586655. DOI: 10.1371/journal.pone.0292961.

NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.

Yi L, Lei Y, Yuan F, Tian C, Chai J, Gu M Sci Rep. 2022; 12(1):10567.

PMID: 35732855 PMC: 9217917. DOI: 10.1038/s41598-022-14575-2.

Late Protective Effect of Netrin-1 in the Murine Acetaminophen Hepatotoxicity Model.

Duan L, Woolbright B, Jaeschke H, Ramachandran A Toxicol Sci. 2020; 175(2):168-181.

PMID: 32207522 PMC: 7253199. DOI: 10.1093/toxsci/kfaa041.

Netrin-4 as a biomarker promotes cell proliferation and invasion in gastric cancer.

Lv B, Song C, Wu L, Zhang Q, Hou D, Chen P Oncotarget. 2015; 6(12):9794-806.

PMID: 25909166 PMC: 4496398. DOI: 10.18632/oncotarget.3400.

References

Kappler J, Franken S, Junghans U, Hoffmann R, Linke T, Muller H . Glycosaminoglycan-binding properties and secondary structure of the C-terminus of netrin-1. Biochem Biophys Res Commun. 2000; 271(2):287-91. DOI: 10.1006/bbrc.2000.2583. View

Hopker V, Shewan D, Tessier-Lavigne M, Poo M, Holt C . Growth-cone attraction to netrin-1 is converted to repulsion by laminin-1. Nature. 1999; 401(6748):69-73. DOI: 10.1038/43441. View

Cirulli V, Beattie G, Klier G, Ellisman M, Ricordi C, Quaranta V . Expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins in the developing pancreas: roles in the adhesion and migration of putative endocrine progenitor cells. J Cell Biol. 2000; 150(6):1445-60. PMC: 2150716. DOI: 10.1083/jcb.150.6.1445. View

Kim S, Hebrok M . Intercellular signals regulating pancreas development and function. Genes Dev. 2001; 15(2):111-27. DOI: 10.1101/gad.859401. View

Trusolino L, Bertotti A, Comoglio P . A signaling adapter function for alpha6beta4 integrin in the control of HGF-dependent invasive growth. Cell. 2001; 107(5):643-54. DOI: 10.1016/s0092-8674(01)00567-0. View

Shekarabi M, Kennedy T . The netrin-1 receptor DCC promotes filopodia formation and cell spreading by activating Cdc42 and Rac1. Mol Cell Neurosci. 2002; 19(1):1-17. DOI: 10.1006/mcne.2001.1075. View

Mu D, Cambier S, Fjellbirkeland L, Baron J, Munger J, Kawakatsu H . The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1. J Cell Biol. 2002; 157(3):493-507. PMC: 2173277. DOI: 10.1083/jcb.200109100. View

Hynes R . Integrins: bidirectional, allosteric signaling machines. Cell. 2002; 110(6):673-87. DOI: 10.1016/s0092-8674(02)00971-6. View

Li X, Meriane M, Triki I, Shekarabi M, Kennedy T, Larose L . The adaptor protein Nck-1 couples the netrin-1 receptor DCC (deleted in colorectal cancer) to the activation of the small GTPase Rac1 through an atypical mechanism. J Biol Chem. 2002; 277(40):37788-97. DOI: 10.1074/jbc.M205428200. View

10.

Wilson M, Scheel D, German M . Gene expression cascades in pancreatic development. Mech Dev. 2002; 120(1):65-80. DOI: 10.1016/s0925-4773(02)00333-7. View

11.

Srinivasan K, Strickland P, Valdes A, Shin G, Hinck L . Netrin-1/neogenin interaction stabilizes multipotent progenitor cap cells during mammary gland morphogenesis. Dev Cell. 2003; 4(3):371-82. DOI: 10.1016/s1534-5807(03)00054-6. View

12.

Charron F, Stein E, Jeong J, McMahon A, Tessier-Lavigne M . The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell. 2003; 113(1):11-23. DOI: 10.1016/s0092-8674(03)00199-5. View

13.

Butler S, Dodd J . A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons. Neuron. 2003; 38(3):389-401. DOI: 10.1016/s0896-6273(03)00254-x. View

14.

Jiang Y, Liu M, Gershon M . Netrins and DCC in the guidance of migrating neural crest-derived cells in the developing bowel and pancreas. Dev Biol. 2003; 258(2):364-84. DOI: 10.1016/s0012-1606(03)00136-2. View

15.

Slorach E, Werb Z . Epithelial morphogenesis: Netrin comes to a sticky and terminal end. Curr Biol. 2003; 13(12):R491-3. DOI: 10.1016/s0960-9822(03)00411-1. View

16.

Nishiyama M, Hoshino A, Tsai L, Henley J, Goshima Y, Tessier-Lavigne M . Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning. Nature. 2003; 423(6943):990-5. DOI: 10.1038/nature01751. View

17.

De Breuck S, Lardon J, Rooman I, Bouwens L . Netrin-1 expression in fetal and regenerating rat pancreas and its effect on the migration of human pancreatic duct and porcine islet precursor cells. Diabetologia. 2003; 46(7):926-33. DOI: 10.1007/s00125-003-1125-5. View

18.

Brigstock D . The CCN family: a new stimulus package. J Endocrinol. 2003; 178(2):169-75. DOI: 10.1677/joe.0.1780169. View

19.

Larrain J, Brown C, De Robertis E . Integrin-alpha3 mediates binding of Chordin to the cell surface and promotes its endocytosis. EMBO Rep. 2003; 4(8):813-8. PMC: 1326342. DOI: 10.1038/sj.embor.embor902. View

20.

Geisbrecht B, Dowd K, Barfield R, Longo P, Leahy D . Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions between DCC and heparin. J Biol Chem. 2003; 278(35):32561-8. DOI: 10.1074/jbc.M302943200. View