Regular readers of this blog will know that we love laminins here. The most interesting* protein family. One of the many reasons that we can confidently say that laminins are really important is that if they don’t function properly the effects are devastating leading to diseases including muscular dystrophy (MDC1A), kidney and eye defects (Pierson syndrome) and skin fragility (junctional epidermolysis bullosa).
In our new mini-review, published in Frontiers in genetics, we describe how the study of these laminin-related disorders has not only increased the understanding of the diseases but also has expanded the fundamental knowledge about how laminin proteins function. This knowledge is now being used to design new therapeutic interventions.
In this review we have focused on laminin-to-laminin interactions, the process by which networks assemble to form coherent structures known as basement membranes.
Lots of specific mutations have been identified that affect this process and these different mutations each affect the outcome for patients in different ways. The effects depend not only on which laminin is mutated and where that laminins is expressed but also how the specific amino acid substitution affect the fold or interaction potential of the protein.
When that information is layered on top of the excellent biochemistry and protein structural work that has been done in parallel to the genetics studies it combines to provide a really rich resource.
In this paper we’ve tried to summarise and combine this information into a concise and easy to digest resource. Our goal with every contribution to the scientific conversation is to add value. Here, bringing all the information together from the different disease types into one place allows trends to be identified that are harder to spot when findings are looked at in isolation. It should, therefore, be very useful for anyone entering the wonderful world of basement membrane biology as well as geneticists and clinicians working on the relevant inherited diseases.
As usual, these things are a group effort. This one was led by two PhD students; Liam Shaw, whose research work directly investigates laminin mutation effects on different aspects of cell and tissue behaviour, and Conor Sugden, whose research is into how disruption of laminin polymerisation affects tissue developmental processes.
This article forms part of a special issue “Molecular Mechanisms of Heritable Connective Tissue Disorders”. The whole issue sounds really interesting. Ours is gold open access so should be accessible for free to all via the link below, but feel free to give me a shout if you can’t get it.
*laminins are the most interesting and important protein family according to the researchers in my lab, although we are on a crusade to widen that feeling!