Deletion of Tetraspanin CD9 Diminishes Lymphangiogenesis in Vivo and in Vitro

Iwasaki, Takeo; Takeda, Yoshito; Maruyama, Kouichi; Yokosaki, Yasuyuki; Tsujino, Kazuyuki; Tetsumoto, Satoshi; Kuhara, Hanako; Nakanishi, Kaori; Otani, Yasushi; Jin, Yingji; Kohmo, Satoshi; Hirata, Haruhiko; Takahashi, Ryōsuke; Suzuki, Mayumi; Inoue, Koji; Nagatomo, Izumi; Goya, Sho; Kijima, Takashi; Kumagai, Toru; Tachibana, Isao; Kawase, Ichiro; Kumanogoh, Atsushi

doi:10.1074/jbc.m112.424291

Cited by 48 publications

(44 citation statements)

References 45 publications

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“…The increased muscle cell fusion observed in their absence has been recapitulated by RNA interference (RNAi)-mediated depletion of CD9P-1, pointing again to the importance of tetraspaninassociated molecules (Charrin et al, 2013). Finally, double CD9 CD81 knockout mice also display a number of pathologies that are not, or only minimally, observed in single-mutant mice, such as pulmonary emphysema (a major pathological component of chronic obstructive pulmonary disease) (Takeda et al, 2008), osteopenia (Takeda et al, 2008) or defects of blood and lymphatic vessels (Iwasaki et al, 2013). …”

Section: The Regulation Of Integrin Function By Cd151 and Other Tetramentioning

confidence: 94%

“…In addition, several tetraspanins, in particular CD9, CD82 and CD151, associate with and/or modulate downstream signalling of tyrosine kinase receptors, including epithelial growth factor receptor (EGFR), ERBB2, c-MET and vascular endothelial growth factor receptor (VEGFR)-3 (also known as FLT4) (Franco et al, 2010;Iwasaki et al, 2013;Murayama et al, 2008;Novitskaya et al, 2014;Odintsova et al, 2003;Sridhar and Miranti, 2006;Takahashi et al, 2007). However, so far, there is no evidence that a particular tetraspanin associates directly with these receptors.…”

Section: Regulation Of Membrane-anchored Enzymes and Growth Factor Simentioning

confidence: 99%

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Tetraspanins at a glance

Charrin

Jouannet

Boucheix

et al. 2014

Journal of Cell Science

370

371

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Tetraspanins are a family of proteins with four transmembrane domains that play a role in many aspects of cell biology and physiology; they are also used by several pathogens for infection and regulate cancer progression. Many tetraspanins associate specifically and directly with a limited number of proteins, and also with other tetraspanins, thereby generating a hierarchical network of interactions. Through these interactions, tetraspanins are believed to have a role in cell and membrane compartmentalization. In this Cell Science at a Glance article and the accompanying poster, we describe the basic principles underlying tetraspaninbased assemblies and highlight examples of how tetraspanins regulate the trafficking and function of their partner proteins that are required for the normal development and function of several organs, including, in humans, the eye, the kidney and the immune system.

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Section: The Regulation Of Integrin Function By Cd151 and Other Tetramentioning

confidence: 94%

Section: Regulation Of Membrane-anchored Enzymes and Growth Factor Simentioning

confidence: 99%

Tetraspanins at a glance

Charrin

Jouannet

Boucheix

et al. 2014

Journal of Cell Science

370

371

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“…Knockout mice for these molecules have not shown serious defects in hematopoiesis, giving some support to the speculation. [66][67][68] CD9, CD32, and CD24 are reported to be expressed by non-MLL-rearranged hematologic malignancies and solid tumors. 65,[69][70][71] Targeting CD24 with antibody resulted in the significant reduction of immortalized lung tumor cells in a xenograft model.…”

Section: Discussionmentioning

confidence: 99%

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Aoki

Watanabe

Saito

et al. 2015

Blood

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“…FAK and Src mediate the activation of small GTPases [18], which are associated with tetraspanins [19,20]. CD151 specifically supports integrin-dependent activation of small GTPases [19,21] and their downstream target ERK1/2 [21], which is also increased by CD9 [22]. Our data reveal that silencing of CD9 or CD151 in J77 T cells, although did not affect CD3 downstream early signaling, reduced the phosphorylation of FAK and ERK1/2 over the conjugation period with Raji/SEE (Fig.…”

Section: Cd9 and Cd151 Contribute To T-cell Activation By Modulating mentioning

confidence: 99%

Tetraspanins CD9 and CD151 at the immune synapse support T‐cell integrin signaling

et al. 2014

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Understanding how the immune response is activated and amplified requires detailed knowledge of the stages in the formation of the immunological synapse (IS) between T lymphocytes and antigen-presenting cells (APCs). We show that tetraspanins CD9 and CD151 congregate at the T-cell side of the IS. Silencing of CD9 or CD151 blunts the IL-2 secretion and expression of the activation marker CD69 by APC-conjugated T lymphocytes, but does not affect the accumulation of CD3 or actin to the IS, or the translocation of the microtubule-organizing center toward the T-B contact area. CD9 or CD151 silencing diminishes the relocalization of α4β1 integrin to the IS and reduces the accumulation of high-affinity β1 integrins at the cell-cell contact. These changes are accompanied by diminished phosphorylation of the integrin downstream targets FAK and ERK1/2. Our results suggest that CD9 and CD151 support integrin-mediated signaling at the IS.Keywords: CD9 r CD151 r Immune synapse r Integrins r T-cell activation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionInteraction between T lymphocytes and antigen-presenting cells (APCs) is critical for antigen presentation and for the initiation of the immune response. This process is characterized by the formation of a dynamic structure called the immune synapse (IS) at the contact between T cells and APCs [1]. At the T cell side of the IS, T-cell receptors (TCRs) and Correspondence: Dr.Francisco Sánchez-Madrid e-mail: fsmadrid@salud.madrid.org associated molecules accumulate in the central area (central supramolecular activation cluster; cSMAC), while adhesion receptors and integrins reorganize in a surrounding external ring called peripheral SMAC (pSMAC) [1]. The increased IS stability enhances T-cell sensitivity, stimulates cytoskeletal processes, induces downstream signaling, and drives effective T-cell differentiation [2,3]. How integrins regulate these processes is not fully understood.Several membrane receptors and integrins concentrated at the IS -CD3, CD4, ICAM-1, lymphocyte function-associated antigen 1 (LFA-1), and very late antigen 4 (VLA-4) -are associated with tetraspanins [4,5] 1968 Rocha-Perugini Vera et al. Eur. J. Immunol. 2014. 44: 1967-1975 organize membrane macrocomplexes called tetraspanin-enriched microdomains (TEMs) [6]. Tetraspanins modulate the function of their associated partners and play important roles in immunity, inflammation, and other processes [6]. Tetraspanins that accumulate at the IS include CD81, which regulates IS architectural organization and maturation [5], and CD82, which contributes to T-cell activation through Rho GTPase-dependent regulation of the actin cytoskeleton [7]. CD82 also increases the adhesion of LFA-1 integrin to its ligand ICAM-1 expressed on APCs [4]. The tetraspanins CD81, CD82, CD53, and CD9 provide T cell costimulatory signals, and CD9 localizes together with TCR signaling molecules in lipid microdomains [4]. Moreover, the T cells of mice deficien...

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Deletion of Tetraspanin CD9 Diminishes Lymphangiogenesis in Vivo and in Vitro

Cited by 48 publications

References 45 publications

Tetraspanins at a glance

Tetraspanins at a glance

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Tetraspanins CD9 and CD151 at the immune synapse support T‐cell integrin signaling

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