Defective filopodia formation is linked to pathologies such as cancer, wherein actively protruding filopodia, at the invasive front, accompany cancer cell dissemination. Despite wide biological significance, delineating filopodia function in complex systems remains challenging and is particularly hindered by lack…
Tensins: Bridging AMP-Activated Protein Kinase with Integrin Activation by Maria Georgiadou et al.
Integrin activation is essential for cell adhesion and for connecting the extracellular matrix to the actin cytoskeleton. Thus, inappropriate integrin activation has been linked to several diseases, including cancer. Recent insights demonstrate that the main fibrillar adhesion component tensin maintains…
A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion by Elisa Närvä et al.
Cell-type-specific functions and identity are tightly regulated by interactions between the cell cytoskeleton and the extracellular matrix (ECM). Human pluripotent stem cells (hPSCs) have ultimate differentiation capacity and exceptionally low-strength ECM contact, yet the organization and function of adhesion sites…
AMPK negatively regulates tensin-dependent integrin activity by Maria Georgiadou et al.
Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the…
SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras by Johanna Lilja et al.
SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with…
Vascular Morphogenesis: An Integrin and Fibronectin Highway by Hellyeh Hamidi et al.
A new study shows that endothelial cells use synaptic-like machinery to control polarized secretion and deposition of newly synthesised fibronectin. This process is coupled to active integrin recycling to the same locations and is fundamental for vascular development in zebrafish.
SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland by Emilia Peuhu et al.
SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly…
L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling by Guillaume Jacquemet et al.
Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer…
Fetal liver endothelium regulates the seeding of tissue-resident macrophages by Pia Rantakari et al.
Macrophages are required for normal embryogenesis, tissue homeostasis and immunity against microorganisms and tumours. Adult tissue-resident macrophages largely originate from long-lived, self-renewing embryonic precursors and not from haematopoietic stem-cell activity in the bone marrow. Although fate-mapping studies have uncovered a…