Table 1.
General Mechanosensors and Mechanosensitive Signaling Pathways
| Mechanosensors | Functions in hematopoiesis |
Interactions | Downstream | References |
|---|---|---|---|---|
| Cell Adhesion Molecules | ||||
| α2β1 Integrin | Homing and homeostasis | Extracellular matrix | p38 MAPK | (Klekotka et al., 2001) |
| α4β1(VLA-4) | Homeostasis | Fibronectin (CS-1) | (Craddock et al., 1997; Papayannopoulou et al., 1995; Potocnik et al., 2000; Williams et al., 1991) | |
| β1 Integrin | Migration | ILK-GSK3β, Wnt, Notch | (Hirsch et al., 1996; Potocnik et al., 2000; Rallis et al., 2010) | |
| VE-cadherin | Proliferation and maintenance | (Fraser et al., 2002; Oberlin et al., 2010) | ||
| N-cadherin | Differentiation | (Hosokawa et al., 2010; Puch et al., 2001) | ||
| Flk- 1/KDR/VEGF2 | Endothelial and hematoendothelial specification | Cell adhesion Shear stress | Src-MAPK, PI3K-Akt eNOS, integrins, small GTPase | (Jalali et al., 1998; Jin et al., 2003; Tzima et al., 2005) |
| G-protein coupled receptors (GPCR) | ||||
| Gαi2 | Erythropoietin modulation | Fluid shear stress | Ca2+ influx, ERK, JNK | (Jo et al., 1997; Miller et al., 1996) |
| EP2 and EP4 Gαs | HSPC self renewal and expansion | PGE2 | cAMP, Wnt/β- catenin, intracellular Ca2+, NOS | (Goessling et al., 2009; Reich and Frangos, 1991; Smalt et al., 1997; Williams et al., 1994) |
| S1PR/EDG1 | Chemoattractant for HSCs and progenitors | Fluid shear stress, Flk- 1/KDR/VEGFR2, protein kinase C | eNOS, Rac GTPase- associated protein CrkII, YAP | (Hughes et al., 2005; Igarashi et al., 2003; Takada et al., 1997; Tanimoto et al., 2002; Venkataraman et al., 2008) |
| CXCR4 | HSC homing and engraftment to the marrow | SDF1-α | Rac1 | (del Pozo et al., 2004; Gu et al., 2003; Ratajczak et al., 2010) |
| CaSR | Cell adhesion and lodgement | Ca2+, Integrins | Integrins | (Adams et al., 2006; Lam et al., 2011; Tharmalingam et al., 2011) |
| Ion channels | ||||
| TRPV4 | Membrane stretching, Polycystin-2 | Ca2+, NO, endothelial reorientation | (Köttgen et al., 2008; Mendoza et al., 2010; Thodeti et al., 2009) | |
| PKD1, PKD2 | Fluid shear stress | Ca2+, NO, HH signaling | (Abou Alaiwi et al., 2009; Hierck et al., 2008; Nauli et al., 2008) | |
| A Disintegrin | ||||
| And Metalloprotease (ADAM) Family | ||||
| ADAM28 | Lymphocyte emigration | α4β1 integrin | Degradation of ECM | (Weber and Saftig, 2012) |
| ADAM8 | Releasing first erythrocytes into the blood stream | Fluid shear stress | Degradation of ECM | (Fourie et al., 2003; Iida et al., 2010) |
| ADAM10 | HSC specification | Notch, Fluid shear stress | NICD | (Gibb et al., 2010; Gibb et al., 2011; Yoda et al., 2011) |
| Nitric Oxide (NO) signaling | ||||
| NOS | Regulation of vascular tone, angiogenesis, endothelial migration and hematopoiesis | Fluid shear stress, Klf2a, PI3K, Notch, Wnt | NO | (Adamo et al., 2009; Davies, 1995; Lucitti et al., 2007; Michurina et al., 2004; North et al., 2009) |
| Other sensors | ||||
| Glycocalyx | HSPS maintenance, differentiation, homing, mobilization | Fluid shear stress | NO, reorganization of the cytoskeleton | (Florian et al., 2003; Hemmorantaa et al., 2007; Thi et al., 2004) |
| Caveolae | Integrins, laminar shear stress | Ca 2+, NO, Ras/Raf/ERK1/2 | (Drab et al., 2001; Rizzo et al., 1998; Wary et al., 1998) | |
| FAK | Hematopoietic lodgment and lineage development | Fluid shear stress | Akt, eNOS | (Glodek et al., 2007; Koshida et al., 2005) |
*
Abbreviations: Flk/KDR/VEGF2 (Fetal liver kinase/Kinase insert domain receptor/Vascular endothelial growth factor), S1PR/EDG1 (Sphingosine 1-phosphate receptor), CXCR4 (chemokine C-X-C motif receptor), CaSR (Calcium sensing receptor), TRPV4 (Transient receptor potential Vallinoid Type 4), PKD (Polycystin), NOS (Nitric oxide synthase), FAK (Focal adhesion kinase)