Neural cell adhesion molecule (N-CAM) is required for cell type segregation and normal ultrastructure in pancreatic islets.
Neural cell adhesion molecule (N-CAM) is required for cell type segregation and normal ultrastructure in pancreatic islets.
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DOI：
10.1083/jcb.144.2.325
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发表时间：
1999-01-25
期刊：
影响因子：
--
通讯作者：
Semb H
中科院分区：
文献类型：
--
作者：
Esni F;Täljedal IB;Perl AK;Cremer H;Christofori G;Semb H
用胚胎组织和培养细胞进行的经典细胞解离/再聚集实验已经确定，由细胞粘附分子介导的细胞内聚性在决定组织和器官内的细胞组织方面是重要的。我们采用N-CAM缺陷小鼠来确定N-CAM是否在胰岛发育过程中对细胞的正确分离起功能性作用。在N-CAM缺陷小鼠中，胰岛外周中产生胰高血糖素的α细胞的正常定位丢失，导致细胞分布更加随机化。与预期的N-CAM缺陷小鼠中细胞-细胞粘附的减少相反，观察到钙粘蛋白、F-肌动蛋白和细胞-细胞连接的聚集显著增加，表明在缺乏适当的N-CAM功能的情况下钙粘蛋白介导的粘附增强。这些数据与胰岛细胞核和Na+/K+-ATP酶的极化分布一起表明胰岛细胞极性也受到影响。最后，β细胞的脱粒表明N-CAM是含胰岛素分泌颗粒正常周转所必需的。两者合计，我们的研究结果证实了在体内的假设，即细胞粘附分子，在这种情况下N-CAM，需要在器官形成过程中的细胞类型分离。这种现象的潜在机制可能包括钙粘蛋白介导的粘附和细胞极性的变化。
Classical cell dissociation/reaggregation experiments with embryonic tissue and cultured cells have established that cellular cohesiveness, mediated by cell adhesion molecules, is important in determining the organization of cells within tissue and organs. We have employed N-CAM-deficient mice to determine whether N-CAM plays a functional role in the proper segregation of cells during the development of islets of Langerhans. In N-CAM-deficient mice the normal localization of glucagon-producing α cells in the periphery of pancreatic islets is lost, resulting in a more randomized cell distribution. In contrast to the expected reduction of cell–cell adhesion in N-CAM-deficient mice, a significant increase in the clustering of cadherins, F-actin, and cell–cell junctions is observed suggesting enhanced cadherin-mediated adhesion in the absence of proper N-CAM function. These data together with the polarized distribution of islet cell nuclei and Na+/K+-ATPase indicate that islet cell polarity is also affected. Finally, degranulation of β cells suggests that N-CAM is required for normal turnover of insulin-containing secretory granules. Taken together, our results confirm in vivo the hypothesis that a cell adhesion molecule, in this case N-CAM, is required for cell type segregation during organogenesis. Possible mechanisms underlying this phenomenon may include changes in cadherin-mediated adhesion and cell polarity.
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影响因子：
16.2
作者：
DODD, J;MORTON, SB;JESSELL, TM
通讯作者：
JESSELL, TM
影响因子：
2.9
作者：
DUMM, CLAG;SEMINO, MC;GAGLIARDINO, JJ
通讯作者：
GAGLIARDINO, JJ
影响因子：
56.9
作者：
CUNNINGHAM, BA;HEMPERLY, JJ;EDELMAN, GM
通讯作者：
EDELMAN, GM
影响因子：
2.7
作者：
Davis, GS;Phillips, HM;Steinberg, MS
通讯作者：
Steinberg, MS
DOI：
10.1073/pnas.89.3.1128
发表时间：
1992-02-01
影响因子：
11.1
作者：
GITTES, GK;RUTTER, WJ
通讯作者：
RUTTER, WJ