Surgical management and results of glenohumeral combination fractures of the anterior glenoid rim and the proximal humerus.

Introduction: The combination of anterior large glenoid rim fractures (GRF) and proximal humerus fractures (PHF) is rare, with limited data available on specific treatments for these glenohumeral combination fractures (GCF). This study aimed to evaluate the treatment approaches for GCF, analyze patient outcomes, and outline surgical management strategies for different fracture types.

Materials And Methods: This retrospective study included patients with GCF, excluding those with fossa glenoidalis fractures, isolated greater tuberosity fractures, or small glenoid rim fractures (< 5 mm).

The role of SPIRE actin nucleators in cellular transport processes.

Looking back at two decades of research on SPIRE actin nucleator proteins, the first decade was clearly dominated by the discovery of SPIRE proteins as founding members of the novel WH2-domain-based actin nucleators, which initiate actin filament assembly through multiple WH2 actin-binding domains. Through complex formation with formins and class 5 myosins, SPIRE proteins coordinate actin filament assembly and myosin motor-dependent force generation. The discovery of SPIRE-regulated cytoplasmic actin filament meshworks in oocytes initiated the next phase of SPIRE research, which has found that SPIRE proteins are integrated in a diverse range of cell biological processes.

Spire1 and Myosin Vc promote Ca-evoked externalization of von Willebrand factor in endothelial cells.

Weibel-Palade bodies (WPB) are endothelial cell-specific storage granules that regulate vascular hemostasis by releasing the platelet adhesion receptor von Willebrand factor (VWF) following stimulation. Fusion of WPB with the plasma membrane is accompanied by the formation of actin rings or coats that support the expulsion of large multimeric VWF fibers. However, factor(s) organizing these actin ring structures have remained elusive.

Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins.

Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that the motor protein myosin-Va works with dynamic actin tracks to drive long-range organelle dispersion in opposition to microtubules. This suggests that in animals, as in yeast and plants, myosin/actin can drive long-range transport.

RELN signaling modulates glioblastoma growth and substrate-dependent migration.

Glioblastoma (GBM) represents the most common and most malignant type of primary brain tumor and significantly contributes to cancer morbidity and mortality. Invasion into the healthy brain parenchyma is a major feature of glioblastoma aggressiveness. Reelin (RELN) is a large secreted extracellular matrix glycoprotein that regulates neuronal migration and positioning in the developing brain and sustains functionality in the adult brain.

Actin assembly mechanisms at a glance.

The actin cytoskeleton and associated motor proteins provide the driving forces for establishing the astonishing morphological diversity and dynamics of mammalian cells. Aside from functions in protruding and contracting cell membranes for motility, differentiation or cell division, the actin cytoskeleton provides forces to shape and move intracellular membranes of organelles and vesicles. To establish the many different actin assembly functions required in time and space, actin nucleators are targeted to specific subcellular compartments, thereby restricting the generation of specific actin filament structures to those sites.

Exploring the iceberg: Prospects of coordinated myosin V and actin assembly functions in transport processes.

Spir actin nucleators and myosin V motor proteins were recently discovered to coexist in a protein complex. The direct interaction allows the coordinated activation of actin motor proteins and actin filament track generation at vesicle membranes. By now the cooperation of myosin V (MyoV) motors and Spir actin nucleation function has only been shown in the exocytic transport of Rab11 vesicles in metaphase mouse oocytes.

A Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion.

Salmonella Typhimurium (S. Tm) is a leading cause of diarrhea. The disease is triggered by pathogen invasion into the gut epithelium.

Coordinated recruitment of Spir actin nucleators and myosin V motors to Rab11 vesicle membranes.

There is growing evidence for a coupling of actin assembly and myosin motor activity in cells. However, mechanisms for recruitment of actin nucleators and motors on specific membrane compartments remain unclear. Here we report how Spir actin nucleators and myosin V motors coordinate their specific membrane recruitment.

Membrane targeting of the Spir·formin actin nucleator complex requires a sequential handshake of polar interactions.

Spir and formin (FMN)-type actin nucleators initiate actin polymerization at vesicular membranes necessary for long range vesicular transport processes. Here we studied in detail the membrane binding properties and protein/protein interactions that govern the assembly of the membrane-associated Spir·FMN complex. Using biomimetic membrane models we show that binding of the C-terminal Spir-2 FYVE-type zinc finger involves both the presence of negatively charged lipids and hydrophobic contributions from the turret loop that intrudes the lipid bilayer.

Orchestration of cell surface proteins by Rab11.

The organization of cells into interconnected structures such as animal tissues requires a sophisticated system directing receptors and adhesion proteins to the cell surface. The Rab11 small G proteins (Rab11a, b, and Rab25) of the Ras superfamily are master regulators of the surface expression of receptors and adhesion proteins. Acting as a molecular switch, Rab11 builds distinct molecular machinery such as motor protein complexes and the exocyst to transport proteins to the cell surface.

Enhanced fear expression in Spir-1 actin organizer mutant mice.

Spir proteins nucleate actin filaments at vesicle membranes and facilitate intracellular transport processes. The mammalian genome encodes two Spir proteins, namely Spir-1 and Spir-2. While the mouse spir-2 gene has a rather broad expression pattern, high levels of spir-1 expression are restricted to the nervous system, oocytes, and testis.

Structural and functional insights into the Spir/formin actin nucleator complex.

The diversity of cellular actin functions is attained by the activation of actin nucleator complexes, which initiate the polymerization of actin monomers into a helical double-stranded filament at defined subcellular compartments. Next to actin functions at the cell membrane, including different forms of membrane protrusions and invaginations, actin dynamics at intracellular membranes has recently become a research focus. Experiments addressing the vesicle-associated Spir WH2 domain containing actin nucleators have provided novel mechanistic insights into the function of actin dynamics at intracellular membranes.

Molecular basis of actin nucleation factor cooperativity: crystal structure of the Spir-1 kinase non-catalytic C-lobe domain (KIND)•formin-2 formin SPIR interaction motif (FSI) complex.

The distinct actin nucleation factors of the Spir and formin subgroup families cooperate in actin nucleation. The Spir/formin cooperativity has been identified to direct two essential steps in mammalian oocyte maturation, the asymmetric spindle positioning and polar body extrusion during meiosis. Understanding the nature and regulation of the Spir/Fmn cooperation is an important requirement to comprehend mammalian reproduction.

Spire-type actin nucleators cooperate with Formin-2 to drive asymmetric oocyte division.

Oocytes mature into eggs by extruding half of their chromosomes in a small cell termed the polar body. Asymmetric oocyte division is essential for fertility [1], but despite its importance, little is known about its mechanism. In mammals, the meiotic spindle initially forms close to the center of the oocyte.

Microtubules as platforms for assaying actin polymerization in vivo.

The actin cytoskeleton is continuously remodeled through cycles of actin filament assembly and disassembly. Filaments are born through nucleation and shaped into supramolecular structures with various essential functions. These range from contractile and protrusive assemblies in muscle and non-muscle cells to actin filament comets propelling vesicles or pathogens through the cytosol.

Actin dynamics at intracellular membranes: the Spir/formin nucleator complex.

The assembly of actin monomers into filaments is a highly regulated basic cellular function. The structural organization of a cell, morphological changes or cell motility is dependent on actin filament dynamics. While within the last decade substantial knowledge has been acquired about actin dynamics at the cell membrane, today only little is known about the actin cytoskeleton and its functions at intracellular endosomal and organelle membranes.

Expression patterns of the mouse Spir-2 actin nucleator.

Spir proteins are the founding members of the novel class of WH2 domain containing actin nucleation factors. They initiate actin polymerization by binding of actin monomers to four WH2 domains in the central part of the proteins. Despite their ability to nucleate actin polymerization in vitro by themselves, Spir proteins form a regulatory complex with the distinct actin nucleators of the formin subgroup of formins.

Identification of a short Spir interaction sequence at the C-terminal end of formin subgroup proteins.

The actin nucleation factors Spire and Cappuccino interact with each other and regulate essential cellular events during Drosophila oogenesis in a cooperative fashion. The interaction blocks formin actin nucleation activity and enhances the Spire activity. Analogous to Spire and Cappuccino, the mammalian homologs Spir-1 and formin-2 show a regulatory interaction.

Regulatory interactions between two actin nucleators, Spire and Cappuccino.

Spire and Cappuccino are actin nucleation factors that are required to establish the polarity of Drosophila melanogaster oocytes. Their mutant phenotypes are nearly identical, and the proteins interact biochemically. We find that the interaction between Spire and Cappuccino family proteins is conserved across metazoan phyla and is mediated by binding of the formin homology 2 (FH2) domain from Cappuccino (or its mammalian homologue formin-2) to the kinase noncatalytic C-lobe domain (KIND) from Spire.

Cellular functions of the Spir actin-nucleation factors.

The initiation of actin polymerization from free monomers requires actin-nucleation factors. Spir proteins nucleate actin polymerization by a novel mechanism that is distinct from actin nucleation by the Arp2/3 complex or by formins. In vitro actin polymerization assays and electron microscopic data show that Spire nucleates actin polymerization by binding four actin monomers to a cluster of four Wiskott-Aldrich syndrome protein-homology domain 2 (WH2) domains in the central region of the proteins.

Very-KIND is a novel nervous system specific guanine nucleotide exchange factor for Ras GTPases.

The kinase non-catalytic c-lobe domain (KIND) evolved from the catalytic protein kinase fold into a potential protein interaction module for signalling proteins. Spir family actin organizers and the non-receptor phosphatase type 13 (PTP type 13) encode a KIND domain in the very N-terminal parts of the proteins. Here we report the characterization and cloning of a third member of the KIND protein family, which we have named very-KIND (VKIND) because of its two KIND domains.

Drosophila Spire is an actin nucleation factor.

The actin cytoskeleton is essential for many cellular functions including shape determination, intracellular transport and locomotion. Previous work has identified two factors--the Arp2/3 complex and the formin family of proteins--that nucleate new actin filaments via different mechanisms. Here we show that the Drosophila protein Spire represents a third class of actin nucleation factor.