Rac1 is Crucial for Hair Follicle Integrity but is Not Essential for Maintenance of the Epidermis

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Sep 1

PMID 16943436

Citations 82

Authors

Anna Chrostek

Xunwei Wu

Fabio Quondamatteo

Rong Hu

Anna Sanecka

Catherin Niemann

Lutz Langbein

Ingo Haase

Cord Brakebusch

Affiliations

Soon will be listed here.

Abstract

Rac1 is a small GTPase that regulates the actin cytoskeleton but also other cellular processes. To investigate the function of Rac1 in skin, we generated mice with a keratinocyte-restricted deletion of the rac1 gene. Rac1-deficient mice lost nearly all of their hair within a few weeks after birth. The nonpermanent part of mutant hair follicles developed constrictions; lost expression of hair follicle-specific keratins, E-cadherin, and alpha6 integrin; and was eventually removed by macrophages. The permanent part of hair follicles and the sebaceous glands were maintained, but no regrowth of full-length hair follicles was observed. In the skin of mutant mice, epidermal keratinocytes showed normal differentiation, proliferation, cell-cell contacts, and basement membrane deposition, demonstrating no obvious defects of Rac1-deficient epidermis in vivo. In vitro, Rac1-null keratinocytes displayed a strong spreading defect and slightly impaired adhesion. These data show that Rac1 plays an important role in sustaining the integrity of the lower part of hair follicles but not in maintenance of the epidermis.

Citing Articles

Rac1 inhibition regenerates wounds in mouse fetuses via altered actin dynamics.

Takaya K, Imbe Y, Wang Q, Okabe K, Sakai S, Aramaki-Hattori N Sci Rep. 2024; 14(1):27213.

PMID: 39516580 PMC: 11549422. DOI: 10.1038/s41598-024-78395-2.

Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry.

Bock F, Dong X, Li S, Viquez O, Sha E, Tantengco M Sci Adv. 2024; 10(6):eadi7840.

PMID: 38324689 PMC: 10849615. DOI: 10.1126/sciadv.adi7840.

The Rho GTPase exchange factor Vav2 promotes extensive age-dependent rewiring of the hair follicle stem cell transcriptome.

Lorenzo-Martin L, Bustelo X Front Cell Dev Biol. 2023; 11:1252834.

PMID: 37822868 PMC: 10562702. DOI: 10.3389/fcell.2023.1252834.

Incongruence between transcriptional and vascular pathophysiological cell states.

Fernandez-Chacon M, Muhleder S, Regano A, Garcia-Ortega L, Rocha S, Torroja C Nat Cardiovasc Res. 2023; 2:2023530-549.

PMID: 37745941 PMC: 7615119. DOI: 10.1038/s44161-023-00272-4.

The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function.

Lorenzo-Martin L, Menacho-Marquez M, Fernandez-Parejo N, Rodriguez-Fdez S, Pascual G, Abad A Oncogene. 2022; 41(24):3341-3354.

PMID: 35534539 PMC: 9187518. DOI: 10.1038/s41388-022-02341-7.

References

Sibilia M, Steinbach J, Stingl L, Aguzzi A, Wagner E . A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor. EMBO J. 1998; 17(3):719-31. PMC: 1170421. DOI: 10.1093/emboj/17.3.719. View

BRAGA V, Machesky L, Hall A, Hotchin N . The small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell-cell contacts. J Cell Biol. 1997; 137(6):1421-31. PMC: 2132529. DOI: 10.1083/jcb.137.6.1421. View

Schmidt-Ullrich R, Paus R . Molecular principles of hair follicle induction and morphogenesis. Bioessays. 2005; 27(3):247-61. DOI: 10.1002/bies.20184. View

Langbein L, Schweizer J . Keratins of the human hair follicle. Int Rev Cytol. 2005; 243:1-78. DOI: 10.1016/S0074-7696(05)43001-6. View

Benitah S, Frye M, Glogauer M, Watt F . Stem cell depletion through epidermal deletion of Rac1. Science. 2005; 309(5736):933-5. DOI: 10.1126/science.1113579. View

Mertens A, Rygiel T, Olivo C, van der Kammen R, Collard J . The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J Cell Biol. 2005; 170(7):1029-37. PMC: 2171536. DOI: 10.1083/jcb.200502129. View

Jaffe A, Hall A . Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005; 21:247-69. DOI: 10.1146/annurev.cellbio.21.020604.150721. View

Osoegawa K, Tateno M, Woon P, Frengen E, Mammoser A, Catanese J . Bacterial artificial chromosome libraries for mouse sequencing and functional analysis. Genome Res. 2000; 10(1):116-28. PMC: 310499. View

Caldelari R, Suter M, Baumann D, de Bruin A, Muller E . Long-term culture of murine epidermal keratinocytes. J Invest Dermatol. 2000; 114(5):1064-5. DOI: 10.1046/j.1523-1747.2000.00960-4.x. View

10.

Brakebusch C, Grose R, Quondamatteo F, Ramirez A, Jorcano J, PIRRO A . Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes. EMBO J. 2000; 19(15):3990-4003. PMC: 306586. DOI: 10.1093/emboj/19.15.3990. View

11.

BRAGA V, Betson M, Li X, Lamarche-Vane N . Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human keratinocytes. Mol Biol Cell. 2000; 11(11):3703-21. PMC: 15031. DOI: 10.1091/mbc.11.11.3703. View

12.

OBrien L, Jou T, Pollack A, Zhang Q, Hansen S, Yurchenco P . Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly. Nat Cell Biol. 2001; 3(9):831-8. DOI: 10.1038/ncb0901-831. View

13.

Langbein L, Rogers M, Praetzel S, Winter H, Schweizer J . K6irs1, K6irs2, K6irs3, and K6irs4 represent the inner-root-sheath-specific type II epithelial keratins of the human hair follicle. J Invest Dermatol. 2003; 120(4):512-22. DOI: 10.1046/j.1523-1747.2003.12087.x. View

14.

Price L, Langeslag M, Ten Klooster J, Hordijk P, Jalink K, Collard J . Calcium signaling regulates translocation and activation of Rac. J Biol Chem. 2003; 278(41):39413-21. DOI: 10.1074/jbc.M302083200. View

15.

Bolis A, Corbetta S, Cioce A, de Curtis I . Differential distribution of Rac1 and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiation. Eur J Neurosci. 2003; 18(9):2417-24. DOI: 10.1046/j.1460-9568.2003.02938.x. View

16.

Wennerberg K, Der C . Rho-family GTPases: it's not only Rac and Rho (and I like it). J Cell Sci. 2004; 117(Pt 8):1301-12. DOI: 10.1242/jcs.01118. View

17.

Ramirez A, Page A, Gandarillas A, Zanet J, Pibre S, Vidal M . A keratin K5Cre transgenic line appropriate for tissue-specific or generalized Cre-mediated recombination. Genesis. 2004; 39(1):52-7. DOI: 10.1002/gene.20025. View

18.

Lauber K, Blumenthal S, Waibel M, Wesselborg S . Clearance of apoptotic cells: getting rid of the corpses. Mol Cell. 2004; 14(3):277-87. DOI: 10.1016/s1097-2765(04)00237-0. View

19.

Delwel G, Hogervorst F, Kuikman I, Paulsson M, Timpl R, Sonnenberg A . Expression and function of the cytoplasmic variants of the integrin alpha 6 subunit in transfected K562 cells. Activation-dependent adhesion and interaction with isoforms of laminin. J Biol Chem. 1993; 268(34):25865-75. View

20.

Sonnenberg A, de Melker A, Martinez de Velasco A, Janssen H, Calafat J, Niessen C . Formation of hemidesmosomes in cells of a transformed murine mammary tumor cell line and mechanisms involved in adherence of these cells to laminin and kalinin. J Cell Sci. 1993; 106 ( Pt 4):1083-102. DOI: 10.1242/jcs.106.4.1083. View