Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

نویسندگان

  • Anna M. Schulz
  • Susanne Stutte
  • Sebastian Hogl
  • Nancy Luckashenak
  • Diana Dudziak
  • Céline Leroy
  • Ignasi Forné
  • Axel Imhof
  • Stephan A. Müller
  • Cord H. Brakebusch
  • Stefan F. Lichtenthaler
  • Thomas Brocker
چکیده

Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 deficiency renders DCs phenotypically mature as they up-regulate the co-stimulatory molecule CD86 from intracellular storages to the cell surface. Cdc42 knockout DCs also accumulate high amounts of invariant chain-major histocompatibility complex (MHC) class II complexes at the cell surface, which cannot efficiently present peptide antigens (Ag's) for priming of Ag-specific CD4 T cells. Proteome analyses showed a significant reduction in lysosomal MHC class II-processing proteins, such as cathepsins, which are lost from DCs by enhanced secretion. As these effects on DCs can be mimicked by chemical actin disruption, our results propose that Cdc42 control of actin dynamics keeps DCs in an immature state, and cessation of Cdc42 activity during DC maturation facilitates secretion as well as rapid up-regulation of intracellular molecules to the cell surface.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Maturation State and Function of Monocyte Derived Dendritic Cells in Liver Transplant Recipients

Background: Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses. Objective: To compare the level of DC maturation and function in liver transplant recipients with healthy controls. Methods: In this study, twelve peripheral blood samples we...

متن کامل

Regulated exocytosis in neuroendocrine cells: a role for subplasmalemmal Cdc42/N-WASP-induced actin filaments.

In neuroendocrine cells, actin reorganization is a prerequisite for regulated exocytosis. Small GTPases, Rho proteins, represent potential candidates coupling actin dynamics to membrane trafficking events. We previously reported that Cdc42 plays an active role in regulated exocytosis in chromaffin cells. The aim of the present work was to dissect the molecular effector pathway integrating Cdc42...

متن کامل

Evaluation of the Immunomodulatory Effect of Curdlan on Maturation and Function of Mouse Spleen-Derived Dendritic Cells

Background: T helper 1 and T helper 17 cells play important roles in immunity against foreign invaders. Differentiation of these Th subsets is affected by state of maturation and cytokines that are produced by dendritic cells (DCs). Curdlan is a linear (1→3)-β- glucan and has shown activity against tumors and infectious agents. Objective: This study aims to investigate whether curdlan plays its...

متن کامل

The small GTPase CDC42 regulates actin dynamics during porcine oocyte maturation

The mammalian oocyte undergoes an asymmetric division during meiotic maturation, producing a small polar body and a haploid gamete. This process involves the dynamics of actin filaments, and the guanosine triphosphatase (GTPase) protein superfamily is a major regulator of actin assembly. In the present study, the small GTPase CDC42 was shown to participate in the meiotic maturation of porcine o...

متن کامل

PICK1 links AMPA receptor stimulation to Cdc42

Rho-family GTPases control numerous cell biological processes via effects on actin dynamics, such as cell migration, cell adhesion, morphogenesis and vesicle traffic. In neurons, they are involved in dendritic spine morphogenesis and other aspects of neuronal morphology via regulation of the actin cytoskeleton. The Rho-family member Cdc42 regulates dendritic spine morphology via its effector N-...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 211  شماره 

صفحات  -

تاریخ انتشار 2015