MOLECULAR & CELLULAR NEUROBIOLOGY 
Master Course Cognitive Neuroscience - Radboud University, Nijmegen

 

INDEX

 INTRODUCTION CELLS AND WITHIN CELLS IN A NUTSHELL GENOMICS MOLECULAR BIOLOGICAL RESEARCH METHODOLOGY NEURODEVELOPMENT  
 

Chapter 2:  Cells and within cells
 

Cells

 DNA and genes

Translation

Receptor Mechanisms
 

    Neurons

    More on DNA

   Proteins, Protein Structure and Protein Analysis

    Ion channel receptors

 

    Glia

   Epigenetics

   Protein folding in the cell

    Tyrosine kinase receptors

Within cells

   Transcription

   Post-translational modifications of proteins

   G-protein-coupled receptors
   Amino ac, Carbohydr, Lipids and Nucleic ac

   Noncoding RNAs

   Protein degradation in the cell - Autophagy

    G-proteins

   Membranes and Membrane Proteins

   miRNAs and the brain

   Protein secretion / Secretory pathway

    Transcription and signalling

   The Exctracellular Matrix

        Transcription factor receptors
 

 

The extracellular matrix                                                                                                                    

 
The extracellular matrix (ECM) is a complex structural entity surrounding and supporting cells that are found within mammalian tissues. The ECM is often referred to as the connective tissue. The ECM is composed of 3 major classes of biomolecules:

1. Structural proteins: collagen and elastin.

2. Specialized proteins: e.g. fibrillin, fibronectin, and laminin.

3. Proteoglycans: these are composed of a protein core to which is attached long chains of repeating disaccharide units termed glycosaminoglycans (GAGs) forming extremely complex high-molecular weight components of the ECM.

 

Collagens

Collagens are the most abundant proteins found in the animal kingdom and the major proteins comprising the ECM. There are at least 30 different collagen genes dispersed through the human genome. These 30 genes generate proteins that combine in a variety of ways to create over 20 different types of collagen fibrils in the various ECMs of the body. Collagens are predominantly synthesized by fibroblasts but epithelial cells also synthesize these proteins. The fundamental higher-order structure of collagens is a long and thin diameter rod-like protein. Collagens are synthesized as longer precursor proteins called procollagens. Collagen fibers begin to assemble in the endoplasmic reticulum (ER) and Golgi complexes. The signal sequence is removed and numerous modifications take place in the collagen chains. Alterations in collagen structure resulting from abnormal genes or abnormal processing of collagen proteins results in numerous diseases.

Fibronectins

The role of fibronectins is to attach cells to a variety of extracellular matrices. Fibronectin attaches cells to all matrices except type IV that involves laminin as the adhesive molecule. Fibronectins are dimers of two similar peptides. At least 20 different fibronectin chains have been identified that arise by alternative RNA splicing of the primary transcript from a single fibronectin gene. Fibronectins contain at least six tightly folded domains each with a high affinity for a different substrate such as heparan sulfate, collagen, fibrin and cell-surface receptors. The cell-surface receptor-binding domain contains a consensus amino acid sequence, RGDS.

Lamina

All basal laminae contain a common set of proteins and GAGs: type IV collagen, heparan sulfate proteoglycans, entactin and laminin. The basal lamina is often refered to as the type IV matrix. Each of the components of the basal lamina is synthesized by the cells that rest upon it. Laminin anchors cell surfaces to the basal lamina.

Representative matrix types produced by vertebrate cells

Collagen Anchor Proteoglycan Cell-Surface Receptor Cells
I fibronectin chondroitin and dermatan sulfates integrin fibroblasts
II fibronectin chondroitin sulfate integrin chondrocytes
III fibronectin heparan sulfate and heparin integrin quiescent hepatocytes, epithelial; assoc. fibroblasts
IV laminin heparan sulfate and heparin laminin receptors all epithelial cells, endothelial cells, regenerating hepatocytes
V fibronectin heparan sulfate and heparin integrin quiescent fibroblasts
VI fibronectin heparan sulfate integrin quiescent fibroblasts

 

 

Mechanisms of ECM function

  

 

 

The versatile functions of the ECM depend on its diverse physical, biochemical, and biomechanical properties. Anchorage to the basement membrane is essential for various biological processes, including asymmetric cell division in stem cell biology and maintenance of tissue polarity (stage 1). Depending on contexts, the ECM may serve to block or facilitate cell migration (stages 2 and 3). In addition, by binding to growth factor signaling molecules and preventing their otherwise free diffusion, the ECM acts as a sink for these signals and helps shape a concentration gradient (stage 4). Certain ECM components, including heparan sulfate proteoglycans and the hyaluronic acid receptor CD44, can selectively bind to different growth factors and function as a signal coreceptor (stage 5) or a presenter (stage 6) and help determine the direction of cell–cell communication. The ECM also direct signals to the cell by using its endogenous growth factor domains (not depicted) or functional fragment derivatives after being processed by proteases such as MMPs (stage 7). Finally, cells directly sense the biomechanical properties of the ECM, including its stiffness, and change a wide variety of behaviors accordingly (stage 8).

 
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