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Review
. 2024 Mar 14:12:1380542.
doi: 10.3389/fcell.2024.1380542. eCollection 2024.

Nidogen in development and disease

Uwe Töpfer  1 , Anne Holz  2
Affiliations
Review

Nidogen in development and disease

Uwe Töpfer et al. Front Cell Dev Biol. .

Abstract

Nidogen, also known as entactin, is a multifunctional glycoprotein that plays a crucial role in the maintenance of the basement membrane (BM), morphogenesis and neuronal plasticity. This review aims to provide an overview of the structural features, molecular interactions and diverse functions associated with Nidogen. As a bridging molecule within the BM, Nidogen acts as a linchpin connecting various extracellular matrix (ECM) components. Its involvement in tissue development, homeostasis, and pathological conditions underscores its biological and medical significance. We discuss the current state of knowledge regarding Nidogen's role in tissue maintenance, cell adhesion, migration, and signaling, shedding light on its intricate contributions to physiological and pathological processes.

Keywords: basement membrane; collagen; dandy-walker malformation; entactin; extracellular matrix; laminin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Molecular structure of Nidogen. (A) Alpha fold-based model of human Nidogen-1 structure. (B) Schematic illustration of the domain structure of human Nidogen-1 and Nidogen-2. Nidogen has three globular domains (G1-G3), which are separated by a short flexible linker region between G1 and G2 and a rod-like domain between G2 and G3. G1 contains a NIDO-domain, while the G2 domain comprises a Nidogen G2 beta-barrel domain and an EGF-like domain, the rod-like domain includes EGF-like domains as well as a Thyroglobulin type-1 domain and the G3 domain is mainly composed of LDL-receptor class B repeats. Interactions with Collagen IV, Perlecan and Laminin are shown with grey arrows. (C) The protein domain structure of Drosophila Nidogen and C. elegans Nidogen shows high similarities with only minor differences in the number of LDL repeats. Notably, invertebrates do not show Thyroglobulin type-1 domains. UniProt database was used for molecular and domain structures (Consortium, 2023).
FIGURE 2
FIGURE 2
Diverse organization levels of Nidogen function during development and disease. (A, B) Nidogen has functions on the macromolecular level in linking the basement membrane (BM) components Laminin and Collagen IV due to the different protein domains. Loss of Nidogen in the Drosophila BM accelerates Collagen IV turnover (A) and results in a micro-perforated BM during embryonic development (B). (C, D) Nidogen plays a crucial role on the level of tissue and organs. Nidogen loss results in branching defects during epithelial morphogenesis (C) and is necessary for maintaining structural integrity in neuromuscular junctions (D). (E, F) The loss of Nidogen is associated with functions on the organismic level such as behavioral changes, including reduced mobility in C. elegans (left) and D. melanogaster larvae (right) (E) and size reduction in various organisms (F). (G, H) The loss of Nidogen has correspondingly serious consequences for the development of various diseases such as Dandy-Walker malformation with occipital encephalocele (G) and soft tissue syndactyly of the extremities in mouse embryos of Nidogen double mutants were phalanges are joined together (H).
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