The cellular function of the MARCKS family of protein kinase C substrates is unknown. In this report, we present evidence that indicates a role for MacMARCKS, a member of the MARCKS family, in the integrin-dependent signal transduction pathways in macrophages. Using a dominant negative mutant of MacMARCKS, we showed that MacMARCKS participates in several integrin-dependent macrophage functions,...

The three-dimensional structure of soluble recombinant integrin avb5 bound to human adenovirus types 2 and 12 (Ad2 and -12) has been determined at ;21-Å resolution by cryoelectron microscopy (cryo-EM). The avb5 integrin is known to promote Ad cell entry. Cryo-EM has shown that the integrin-binding RGD (ArgGly-Asp) protrusion of the Ad2 penton base protein is highly mobile (P. L. Stewart, C. Y. ...

Dystrophin Dp71 is the main product of the Duchenne muscular dystrophy gene in the brain; however, its function is unknown. To study the role of Dp71 in neuronal cells, we previously generated by antisense treatment PC12 neuronal cell clones with decreased Dp71 expression (antisense-Dp71 cells). PC12 cells express two different splicing isoforms of Dp71, a cytoplasmic variant called Dp71f and a...

We show that loss of beta1 integrin function affects connexin (Cx) expression in embryonic stem (ES) cell-derived cardiomyocytes. Both loss of beta1 integrin function and inhibition of integrin clustering by RGD peptides in wild type ES cells correlated with upregulated expression of gap junctional proteins in ES-derived cardiomyocytes. The upregulation of connexin transcript levels in beta1 in...

Memory consolidation theory posits that newly acquired information passes through a series of stabilization steps before being firmly encoded. We report here that in rat and mouse, hippocampus cell adhesion receptors belonging to the β1-integrin family exhibit dynamic properties in adult synapses and that these contribute importantly to a previously unidentified stage of consolidation. Quantita...

The clustering of acetylcholine receptors (AChR) on skeletal muscle fibers is an early event in the formation of neuromuscular junctions. Recent studies show that laminin as well as agrin can induce AChR clustering. Since the alpha7beta1 integrin is a major laminin receptor in skeletal muscle, we determined if this integrin participates in laminin and/or agrin-induced AChR clustering. The alter...

The integrin family plays a major role in complex biological events such as differentiation, development, wound healing, and the altered adhesive and invasive properties of tumor cells. Integrin (alpha5beta1 is a classical fibronectin receptor, and it has been known as a tumor suppressor gene because tumor cells overexpressing alpha5beta1 are less tumorigenic than their parent cells. However, t...

SHANK-associated RH domain interactor (SHARPIN) inhibits integrins through interaction with the integrin α-subunit. In addition, SHARPIN enhances nuclear factor-kappaB (NF-κB) activity as a component of the linear ubiquitin chain assembly complex (LUBAC). However, it is currently unclear how regulation of these seemingly different roles is coordinated. Here, we show that SHARPIN binds integrin ...

Integrin activation is an indispensable step for various integrin-mediated biological functions. Kindlin-2 is known to coactivate integrins with Talin; however, molecules that restrict integrin activation are elusive. Here, we demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2 protein in cells and hinders integrin activation. Smurf1 interacts with and promotes Kind...

LRP-1 is a large endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP-1 was reported to control focal adhesion turnover to optimize the adhesion-deadhesion balance to support invasion. To better understand how LRP-1 coordinates cell-extracellular matrix interface, we explored its ability to regulate cell surface integrins in thyroid carcinomas. Usin...