Distinct domains in the matricellular protein Lonely heart are crucial for cardiac extracellular matrix formation and heart function in Drosophila

Abstract

The biomechanical properties of extracellular matrices (ECMs) are critical to many biological processes, including cell-cell communication and cell migration and function. The correct balance between stiffness and elasticity is essential to the function of numerous tissues, including blood vessels and the lymphatic system, and depends on ECM constituents (the "matrisome") and on their level of interconnection. However, despite its physiological relevance, the matrisome composition and organization remain poorly understood. Previously, we reported that the ADAMTS-like protein Lonely heart (Loh) is critical for recruiting the type IV collagen-like protein Pericardin to the cardiac ECM. Here, we utilized as a simple and genetically amenable invertebrate model for studying Loh-mediated recruitment of tissue-specific ECM components such as Pericardin to the ECM. We focused on the functional relevance of distinct Loh domains to protein localization and Pericardin recruitment. Analysis of Loh deletion constructs revealed that one thrombospondin type 1 repeat (TSR1-1), which has an embedded WW motif, is critical for anchoring Loh to the ECM. Two other thrombospondin repeats, TSR1-2 and TSR1-4, the latter containing a CTCG motif, appeared to be dispensable for tethering Loh to the ECM but were crucial for proper interaction with and recruitment of Pericardin. Moreover, our results also suggested that Pericardin in the cardiac ECM primarily ensures the structural integrity of the heart, rather than increasing tissue flexibility. In conclusion, our work provides new insights into the roles of thrombospondin type 1 repeats and advances our understanding of cardiac ECM assembly and function.

APC/CFzr regulates cardiac and myoblast cell numbers, and plays a crucial role during myoblast fusion

“…It is formed by CBs that differentiate into contractile cardiomyocytes by the end of embryogenesis. The heart is attached to a heterogeneous group of PCs via a specialised extracellular matrix (ECM) (Drechsler et al, 2013;Volk et al, 2014;Rotstein et al, 2018;Wilmes et al 2018). While cardiomyocytes provide the contractile forces to pump hemolymph through the body, the role of PCs is more complex.…”

Biosynthesis and assembly of the Collagen IV-like protein Pericardin inDrosophila melanogaster

“…In contrast to the ubiquitously distributed Collagen IV, Pericardin assembles specifically within distinct matrices: these include the matrix of the heart tube, the surface of pericardial cells and oenocytes, and the cap cells of chordotonal organs. Lack of Pericardin, or its ECM adapter protein Lonely heart (Loh), causes heart failure upon ageing ( Drechsler et al, 2013 ; Rotstein et al, in revision ). During development, Pericardin is synthesised and secreted by different tissues: first, during embryogenesis, the pericardial cells secrete Pericardin; later, in first and second instar larvae, the main source of Pericardin secretion is the adipocytes.…”

Three-Dimensional Culture of Rhipicephalus (Boophilus) microplus BmVIII-SCC Cells on Multiple Synthetic Scaffold Systems and in Rotating Bioreactors

“…Radiating strands of biomaterial attaching to adjacent nanofiber strands (Figure 6) are also suggestive of ECM, which is also observed in association with in vivo mammalian parenchymal tissue [82][83][84][85]. The aforementioned sheet-like material covering underlying cells suggests that cellular interactions and secretion of ECM-like material are facilitated by growth in the 3-D microenvironments, which had not been reported for BmVIII-SCC cells in 2-D culture.…”