Hemicentin-mediated type IV collagen assembly strengthens juxtaposed basement membrane linkage.
Hemicentin-mediated type IV collagen assembly strengthens juxtaposed basement membrane linkage.
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DOI：
10.1083/jcb.202112096
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发表时间：
2023-01-02
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--
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通过连接并列的基底膜(BMS)进行组织附着对许多器官的结构和功能至关重要。Gianakas等人。确定半胱氨酸和纤毛蛋白-1在启动BM-BM附着中的关键作用，以及IV型胶原在稳定这种连接并使其能够抵抗高机械负荷中的关键作用。基底膜(BM)基质包围和分隔大部分组织。然而，通过鲜为人知的机制，邻近组织的骨髓基质也可以稳定地连接到支持器官结构和功能的地方。利用内源敲入荧光蛋白、条件RNAi、光遗传学和定量活成像技术，我们在秀丽线虫产卵期间支持子宫的子宫和表皮缝隙细胞BMS之间鉴定了介导BM连锁(B-link)的细胞外基质蛋白。我们发现，半球蛋白是由USE分泌的，并促进纤维蛋白-1的组装，共同启动B-连接。然而，在产卵期间，这两种蛋白质的水平都会下降，并不是维持B-连接所必需的。相反，我们发现Semicentin招募ADAMTS9/20，这有助于组装高水平的IV型胶原，在机械活跃的产蛋期维持B-link。这项工作揭示了BM-BM连接成熟的机制，并确定了半边蛋白和纤毛蛋白-1在启动连接过程中的关键功能，以及IV型胶原在加强这种特殊形式的组织连接中的作用。
Tissue attachment through linking juxtaposed basement membranes (BMs) is crucial for the structure and function of many organs. Gianakas et al. identify a key role for hemicentin and fibulin-1 in initiating BM–BM attachment and type IV collagen in stabilizing this linkage and allowing it to resist high mechanical loads. Basement membrane (BM) matrices surround and separate most tissues. However, through poorly understood mechanisms, BMs of adjacent tissue can also stably link to support organ structure and function. Using endogenous knock-in fluorescent proteins, conditional RNAi, optogenetics, and quantitative live imaging, we identified extracellular matrix proteins mediating a BM linkage (B-LINK) between the uterine utse and epidermal seam cell BMs in Caenorhabditis elegans that supports the uterus during egg-laying. We found that hemicentin is secreted by the utse and promotes fibulin-1 assembly to jointly initiate the B-LINK. During egg-laying, however, both proteins’ levels decline and are not required for B-LINK maintenance. Instead, we discovered that hemicentin recruits ADAMTS9/20, which facilitates the assembly of high levels of type IV collagen that sustains the B-LINK during the mechanically active egg-laying period. This work reveals mechanisms underlying BM–BM linkage maturation and identifies a crucial function for hemicentin and fibulin-1 in initiating attachment and type IV collagen in strengthening this specialized form of tissue linkage.
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