Structural Characterization of the Extracellular Domain of CASPR2 and Insights into Its Association with the Novel Ligand Contactin1

Contactin-associated protein-like 2 (CNTNAP2) encodes for CASPR2, a multidomain single transmembrane protein belonging to the neurexin superfamily that has been implicated in a broad range of human phenotypes including autism and language impairment. Using a combination of biophysical techniques, including small angle x-ray scattering, single particle electron microscopy, analytical ultracentrifugation, and bio-layer interferometry, we present novel structural and functional data that relate the architecture of the extracellular domain of CASPR2 to a previously unknown ligand, Contactin1 (CNTN1). Structurally, CASPR2 is highly glycosylated and has an overall compact architecture. Functionally, we show that CASPR2 associates with micromolar affinity with CNTN1 but, under the same conditions, it does not interact with any of the other members of the contactin family. Moreover, by using dissociated hippocampal neurons we show that microbeads loaded with CASPR2, but not with a deletion mutant, co-localize with transfected CNTN1, suggesting that CNTN1 is an endogenous ligand for CASPR2. These data provide novel insights into the structure and function of CASPR2, suggesting a complex role of CASPR2 in the nervous system

Möglichkeiten zur Optimierung der Wirkungsweise bauchemischer Zusatzmittel durch Mechanismen der kontrollierten Wirkstofffreisetzung

Zugleich: Dissertation, Technische Universität Berlin, 201

Versatile triggered substance release systems via a highly flexible high throughput encapsulation technique

Herein, a new high speed process for microcapsule generation in the field of medium-to-large-size capsules (0.2–5 mm) is reported which is rendered possible by combining three basic processing techniques in one system, namely the coextrusion technique, the vibrational nozzle technique and UV-curing. The versatility of the process is impressing, when it is combined with suitable materials. This is demonstrated for controlled release systems for concrete additives (superplasticizers) based on core–shell as well as matrix-type morphology that are assembled herein. It is shown that the process is highly flexible with respect to the material that can be encapsulated and, moreover, highly adjustable with respect to release mechanisms as these can be steered via the flexible choice of the shell materials. Eventually, the capsules can be created in a highly robust way and at remarkable throughput speed

Effect of olivine nano-silica additions on the fresh and hardened behaviour of cement pastes and mortars

The present research aims on elucidating the effects of OnS in the fresh and hardened state of cement pastes and standard mortars. To study the effects of OnS and superplasticizer (SP), rheological measurements and the mini-spread flow test were carried out to assess changes in the viscosity caused by the volumetric substitutions of cement (0.5, 1.5, 3.0, 4.5, 7.0 and 10%). The rheological tests were complemented with isothermal calorimetric measurements and standard tests on the compressive and flexural strength of mortars. The results obtained demonstrated that the addition of OnS increases the viscosity, the yield point and the hydration degree of the cement paste, mainly due to the increase of the total specific surface area. This holds also for the case in which a fix amount of SP is applied. The mechanical tests demonstrated that the optimum amount of OnS in standard mortars to obtain an improvement is between 1.5 and 3.0% by vol. Based on the analysis performed, it was possible to conclude that the OnS acts as an accelerating and pozzolanic agent in concrete

A proteomic screen of neuronal cell-surface molecules reveals iglons as structurally conserved interaction modules at the synapse

In the developing brain, cell-surface proteins play crucial roles, but their protein-protein interaction network remains largely unknown. A proteomic screen identified 200 interactions, 89 of which were not previously published. Among these interactions, we find that the IgLONs, a family of five cell-surface neuronal proteins implicated in various human disorders, interact as homo- and heterodimers. We reveal their interaction patterns and report the dimeric crystal structures of Neurotrimin (NTRI), IgLON5, and the neuronal growth regulator 1 (NEGR1)/IgLON5 complex. We show that IgLONs maintain an extended conformation and that their dimerization occurs through the first Ig domain of each monomer and is Ca2+ independent. Cell aggregation shows that NTRI and NEGR1 homo- and heterodimerize in trans. Taken together, we report 89 unpublished cell-surface ligand-receptor pairs and describe structural models of trans interactions of IgLONs, showing that their structures are compatible with a model of interaction across the synaptic cleft. Many aspects of synapse formation, specification, and maturation rely on interactions among a rich repertoire of cell-surface glycoproteins with adhesive and repulsive properties. Although the identity of these proteins is known, their network of interactions remains largely untapped. Ranaivoson et al. have identified a number of protein-protein interactions and have determined the structures of three members of the IgLONs, a family of five proteins of the immunoglobulin superfamily that has recently been implicated in a wide range of human disease