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…
The complexity of integrins in cancer and new scopes for therapeutic targeting by Hellyeh Hamidi et al.
Cancer is a complex disease and progresses within a dynamically evolving extracellular matrix that controls virtually every aspect of the tumour and tumour-associated cells. Interactions with the extracellular microenvironment are predominately mediated by a family of cell-surface transmembrane receptors called…
Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription by Riina Kaukonen et al.
Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific contribution of the matrix…
Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-β-Slug signaling by Fang Cheng et al.
Vimentin has been shown to be involved in wound healing, but its functional contribution to this process is poorly understood. Here we describe a previously unrecognized function of vimentin in coordinating fibroblast proliferation and keratinocyte differentiation during wound healing. Loss…