Tetraspanin 33 (TSPAN33) regulates endocytosis and migration of human B lymphocytes by affecting the tension of the plasma membrane.,The FEBS Journal

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Tetraspanin 33 (TSPAN33) regulates endocytosis and migration of human B lymphocytes by affecting the tension of the plasma membrane.
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-01-20 , DOI: 10.1111/febs.15216
Itze C Navarro-Hernandez _{1,

2} , Orestes López-Ortega ₃ , Ernesto Acevedo-Ochoa _{1,

4} , Rodrigo Cervantes-Díaz _{1,

5} , Sandra Romero-Ramírez _{1,

5} , Víctor A Sosa-Hernández _{1,

3} , David E Meza-Sánchez ₁ , Guillermo Juárez-Vega ₁ , César A Pérez-Martínez ₃ , Bibiana Chávez-Munguía ₆ , Arturo Galván-Hernández ₇ , Armando Antillón ₇ , Iván Ortega-Blake ₇ , Leopoldo Santos-Argumedo ₃ , José M Hernández-Hernández ₂ , José L Maravillas-Montero ₁

Affiliation

B lymphocytes are a leukocyte subset capable of developing several functions apart from differentiating into antibody‐secreting cells. These processes are triggered by external activation signals that induce changes in the plasma membrane properties, regulated by the formation of different lipid‐bilayer subdomains that are associated with the underlying cytoskeleton through different linker molecules, thus allowing the functional specialization of regions within the membrane. Among these, there are tetraspanin‐enriched domains. Tetraspanins constitute a superfamily of transmembrane proteins that establish lateral associations with other molecules, determining its activity and localization. In this study, we identified TSPAN33 as an active player during B‐lymphocyte cytoskeleton and plasma membrane‐related phenomena, including protrusion formation, adhesion, phagocytosis, and cell motility. By using an overexpression model of TSPAN33 in human Raji cells, we detected a specific distribution of this protein that includes membrane microvilli, the Golgi apparatus, and extracellular vesicles. Additionally, we identified diminished phagocytic ability and altered cell adhesion properties due to the aberrant expression of integrins. Accordingly, these cells presented an enhanced migratory phenotype, as shown by its augmented chemotaxis and invasion rates. When we evaluated the mechanic response of cells during fibronectin‐induced spreading, we found that TSPAN33 expression inhibited changes in roughness and membrane tension. Contrariwise, TSPAN33 knockdown cells displayed opposite phenotypes to those observed in the overexpression model. Altogether, our data indicate that TSPAN33 represents a regulatory element of the adhesion and migration of B lymphocytes, suggesting a novel implication of this tetraspanin in the control of the mechanical properties of their plasma membrane.

中文翻译：

四跨膜蛋白33（TSPAN33）通过影响质膜的张力来调节人B淋巴细胞的内吞作用和迁移。

B淋巴细胞是一种白细胞亚群，除了分化成分泌抗体的细胞外，还具有多种功能。这些过程是由外部激活信号触发的，该信号引起质膜特性的变化，并通过不同的脂质分子亚结构域的调节来调节，这些亚结构域通过不同的接头分子与基础细胞骨架相关联，从而允许膜内区域的功能特化。其中，有富含四跨素的结构域。四跨膜蛋白构成跨膜蛋白的超家族，跨膜蛋白与其他分子建立横向关联，从而决定其活性和定位。在这项研究中，我们确定TSPAN33是B淋巴细胞细胞骨架和质膜相关现象（包括突起形成，粘附，吞噬作用和细胞运动。通过在人类Raji细胞中使用TSPAN33的过表达模型，我们检测到了该蛋白的特定分布，包括膜微绒毛，高尔基体和细胞外囊泡。另外，我们发现由于整联蛋白的异常表达，吞噬能力降低，细胞粘附特性改变。因此，这些细胞表现出增强的迁徙表型，如其增加的趋化性和侵袭率所示。当我们评估纤连蛋白诱导的扩散过程中细胞的机械反应时，我们发现TSPAN33的表达抑制了粗糙度和膜张力的变化。相反，TSPAN33敲低细胞表现出与在过表达模型中观察到的相反的表型。共，

更新日期：2020-01-20

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