Classically Activated Macrophages Use Stable Microtubules for Matrix Metalloproteinase-9 (MMP-9) Secretion

Hanania, Raed; Sun, He; Xu, Kewei; Pustylnik, Sofia; Jeganathan, Sujeeve; Harrison, Rene E.

doi:10.1074/jbc.m111.290676

Cited by 100 publications

(101 citation statements)

References 71 publications

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“…The lack of cell proliferation in ZnT2-null mice suggests that loss of ZnT2 in macrophages may not be able to support normal epithelial and fibroblast proliferation. Because MMP-9 expression was greater in ZnT2-null mice, one explanation may be that the loss of ZnT2 hyperactivates macrophages (25), which can stimulate tumor growth factor-␤ signaling pathway and impair ductal outgrowth (65,66). Additionally, adipocyte hypertrophy combined with abnormal macrophage activation may be indicative of an inflammatory mammary gland that in turn interrupts optimal mammary development (67,68).…”

Section: Discussionmentioning

confidence: 99%

“…1F; Ref. 25). Importantly, there was no significant effect on plasma (wt, 12.13 mol/liter Ϯ 1.4; ZnT2ko, 11.14 mol/liter Ϯ 1.9), liver (wt, 29.33 g Zn/g of tissue Ϯ 3.2; ZnT2ko, 28.07 g Zn/g of tissue Ϯ 3.1) or mammary gland (wt, 11.44 g Zn/g of tissue Ϯ 1.3; ZnT2ko, 11.15 g Zn/g of tissue Ϯ 1.8) zinc concentrations.…”

Section: Nulliparous Znt2-null Mice Have Reduced Mammary Ductal Invasmentioning

confidence: 99%

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Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

Lee

Hennigar

Alam

et al. 2015

Journal of Biological Chemistry

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Background: ZnT2 is expressed in non-secreting and secreting mammary epithelium; however, the physiological role is not understood. Results: ZnT2-null mice have impaired mammary expansion and compromised mammary differentiation and milk secretion during lactation. Conclusion: ZnT2-mediated zinc transport is critical for mammary development and function during lactation. Significance: This study identifies novel consequences of ZnT2 function in the mammary gland.

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Section: Discussionmentioning

confidence: 99%

Section: Nulliparous Znt2-null Mice Have Reduced Mammary Ductal Invasmentioning

confidence: 99%

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

Lee

Hennigar

Alam

et al. 2015

Journal of Biological Chemistry

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“…Rab3B and Rab3D are implicated in processes not directly related to control of exocytosis, including the regulation of catecholamine uptake into SGs, 46 receptor transcytosis, 47 SG-microtubule interactions, 48 and SG maturation. 49 The function of Rab3s on WPBs remains to be established.…”

Section: Rab27a Effectors and Vwf Secretion 2765mentioning

confidence: 99%

The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis

Bierings

Hellen

Kiskin

et al. 2012

Blood

166

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Weibel-Palade body (WPB) exocytosis underlies hormone-evoked VWF secretion from endothelial cells (ECs). We identify new endogenous components of the WPB: Rab3B, Rab3D, and the Rab27A/ Rab3 effector Slp4-a (granuphilin), and determine their role in WPB exocytosis. We show that Rab3B, Rab3D, and Rab27A contribute to Slp4-a localization to WPBs. siRNA knockdown of Slp4-a, MyRIP, Rab3B, Rab3D, Rab27A, or Rab3B/ Rab27A, or overexpression of EGFPSlp4-a or EGFP-MyRIP showed that Slp4-a is a positive and MyRIP a negative regulator of WPB exocytosis and that Rab27A alone mediates these effects. We found that ECs maintain a constant amount of cellular Rab27A irrespective of the WPB pool size and that Rab27A (and Rab3s) cycle between WPBs and a cytosolic pool. The dynamic redistribution of Rab proteins markedly decreased the Rab27A concentration on individual WPBs with increasing WPB number per cell. Despite this, the probability of WPB release was independent of WPB pool size showing that WPB exocytosis is not determined simply by the absolute amount of Rab27A and its effectors on WPBs. Instead, we propose that the probability of release is determined by the fractional occupancy of WPB-Rab27A by Slp4-a and MyRIP, with the balance favoring exocytosis. (Blood. 2012;120(13):2757-2767) IntroductionHormone-evoked VWF secretion from endothelial cells (ECs) is mediated by exocytosis of specialized secretory granules (SGs) called Weibel-Palade bodies (WPBs). 1 WPB exocytosis is triggered by increases in intracellular free Ca 2ϩ or cAMP concentrations, and involves a number of molecular components, including the Nethylmaleimide-sensitive factor, VAMP3, SNAP23, syntaxin 4, RalA, the annexin A2/S100A10 complex, and phospholipase D. [2][3][4][5][6][7] In addition, Rab proteins also regulate WPB exocytosis. A subset of Rab proteins, including Rab3A-3D, Rab27A/B, and Rab37, is associated with SGs in different cell types where they regulate SG biogenesis, trafficking, and exocytosis. 8 Secretory cells often express a mixture of these "secretory" Rabs, which may have overlapping or distinct functions. Human ECs are reported to express mRNA for Rab3A, Rab3D, and Rab37,3,9,10 Rab3B protein, 11 and Rab27A mRNA and protein. 12,13 To date, Rab27A is the only endogenous EC Rab protein that has been detected on WPBs. Through its effector MyRIP and Myosin Va, Rab27A is proposed to negatively regulate WPB exocytosis. 13,14 Rab27A can interact with different effector molecules, and many secretory cells express a mixture of these effectors. 8 In these cases, SG exocytosis probably depends on the balance of Rab27A interactions with the complement of Rab effectors in the cell.In addition to MyRIP, ECs contain mRNA for the Rab27A effector Slp4-a (granuphilin). 13 Slp4-a links SGs to the plasma membrane (PM) through SG-associated Rab proteins (principally Rab27A), PM-associated syntaxins (1a, 2, or 3) and soluble Munc18 isoforms. [15][16][17][18][19] Syntaxins exist in open and closed conformations that determine their participation in SNARE complex f...

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“…The kinesin 2 molecular motor is known to participate to "non intraflagellar" transport in the cell, like retrograde traffic between the Golgi and the endoplasmic reticulum (ER) (Stauber et al 2006), endosome and lysosome transports (Bananis et al 2004;Brown et al 2005), endocytosis and recycling of cell surface receptors like transferrin, cubulin and megalin receptors, or of other proteins like Clc-5, the H + /Cl − exchange transporter (Schonteich et al 2008;Reed et al 2010). The KIF3 molecular motor also plays an important role in the transport of vesicles containing GluR2 and GLUT4 receptors or MT1-MMP and MMP-9 metalloproteinases from the cytosol to the plasma membrane (Imamura et al 2003;Wiesner et al 2010;Hanania et al 2012;Lin et al 2012). Unfortunately, we were unable to analyze the intracellular traffic or the cell surface expression of the TSH receptor in vivo or in vitro, due to the lack of specific antibody working on tissue sections (and probably also to the very low expression of the TSH receptor at the thyrocyte surface) and the unexpected consequence of Kif3a inactivation on TSH receptor expression directed by lentivirus infection.…”

Section: Discussionmentioning

confidence: 99%

Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism

D’Amico¹,

Gayral²,

Massart³

et al. 2014

EJEA

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Kinesins, including the kinesin 2/KIF3 molecular motor, play an important role in intracellular traffic and can deliver vesicles to distal axon terminal, to cilia, to non-polarized cell surface or to epithelial cell basolateral membrane, thus taking part to the establishment of cellular polarity. We report here the consequences of the kinesin 2 motor inactivation in the thyroid of 3 week-old Kif3a Δ/flox Pax8 Cre/+ mutant mice. Our results indicate first that 3 week-old Pax8 Cre/+ mice used in these experiments present minor thyroid functional defects resulting in a slight increase in circulating bioactive TSH and intracellular cAMP levels, sufficient to maintain blood T4 levels in the normal range. Second, Kif3a inactivation in thyrocytes markedly amplified the phenotype observed in Pax8 Cre/+ mice, resulting in an altered TSH signaling upstream of the second messenger cAMP and mild hypothyroidism. Finally, our results in mouse embryonic fibroblasts

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Classically Activated Macrophages Use Stable Microtubules for Matrix Metalloproteinase-9 (MMP-9) Secretion

Cited by 100 publications

References 71 publications

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis

Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism

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