Figure 3.
Basement membrane signaling cascade. Basement membrane core molecules—laminin, type IV collagen, perlecan, and nidogen—regulate cell adhesion, migration, polarization, proliferation, and differentiation via directly or indirectly binding to cell surface receptors such as dystroglycan (DG), integrin, receptor tyrosine kinase (RTK), and discoidin domain receptor 1 (DDR1). For example, laminin-6 plays a role in mechanical signaling transduction by assembling into multi-molecular fibrillary complexes with perlecan via a DG-dependent and integrin-independent manner.137 Laminin binding to DG also triggers the GRB2 (growth factor receptor-bound protein 2)-RAC1-PAK1-JNK (c-Jun N-terminal kinase) pathway that contributes to hypertrophy.138 Evidence shows a direct connection between DG and MAP kinase (MEK) and between DG and extracellular signal-regulated kinase (ERK).139 Type IV collagen plays a role by interacting with the laminin network through perlecan and nidogen followed by binding with integrins and DDR1.76 Perlecan modulates cell survival, migration, and proliferation by tethering growth factors.15,140 By binding to laminin and type IV collagen, nidogen plays a role in maintaining capillary integrity through forming a non-covalent high-affinity stabilizing bridge.76