Updated: 3/7/2019

Cell Surface Proteins

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Overview
  •  Purpose This illustration highlights the basic various types of cell-cell adhesion protein
    • allow cells to attach to each other
      • via different types of cell-cell junctions
    • allow cells to attach to the basement membrane
      • complex interaction between cells and supporting matrix
      • two divisions
        • basal lamina - provides attachment for most types of epithelium
          • composition
            • type IV collagen
            • laminin
            • heparan sulfate
        • reticular lamina - supports lymphoid and adipose tissues
          • composition
            • type III collagen (reticular fibers)
  • Types of molecules
    • cadherin
      • structure
        • calcium dependent
        • binds cadherin dimer on another cell extracellularly
        • binds actin intracellularly (via catenin)
      • function
        • ↑ cell-cell binding
          • cadherin receptor ↓ regulated in cancer metastasis
    • selectin
      • calcium dependent
      • function
        • binds carbohydrates in cell-cell interactions
      • subtypes
        • L-selectin
          • on leukocytes
          • L-selectins have Sialyl-Lewis glycoproteins as ligands
        • P-selectin
          • on platelets and endothelial cells
        • E-selectin
          • on endothelial cells
          • binds leukocytes strongly
            • ↑ expression on surface during acute inflammatory response
              • stimulated by TNF-α
        • LAD II is caused by a defective selectin ligand
          • impaired interaction with E- and P- selectins on endothelium
            • causes a rolling defect
            • presents with recurrent bacterial infections with psychomotor and mental retardation
    • integrin
      • structure
        • calcium-independent
        • transmembrane
        • binds fibronectin and laminin extracellularly
        • binds actin intracellularly
      • function
        • binds leukocytes
          • neutrophilic attachment in adhesion via an integrin LFA-1
          • defective in leukocyte adhesion deficiency (LAD) type I
            • interaction with ICAM and VCAM impaired
            • causes an adhesion defect
            • presents with recurrent bacterial infections and delayed loss of umbilicus postpartum
        • bind to laminin in ECM
          • integrin receptor ↑ regulated in cancer metastasis
Types of Cell-Cell Junctions
  • Tight junctions This illustration highlights the major types of cell junction proteins
    • aka zonula occludens
    • structure 
      • zona occuldens (ZOs) 1, 2, 3
      • claudin proteins
      • membrane spanning proteins
        • bind cellA actin intracellularly on one end
        • bind cellB actin intracellularly on opposite end
    • location
      • apical end of epithelial cells
    • function
      • prevent diffusion
      • create cell membrane polarity
  • Adherens junctions
    • aka zonula adherens
    • structure
      • cadherin proteins
        • Ca2+-dependent adherin = cadherin
    • location
      • belt around cell
        • below tight junction
  • Desmosomes
    • aka macula adherens
    • structure
      • cadherin proteins
        • link between two cells
        • attach to intermediate filaments
      • keratin and desmoplakin proteins
    • location
      • distinct sites
    • function
      • rivets
      • gives strength to junction between cells
    • clinical importance 
      • pemphigus vulgaris
        • pathophysiology
          • auto-IgG against desmosomal proteins in keratinocytes
          • type II hypersensitivity
        • presentation
          • painful, flaccid vesicles form on skin and oral mucosae
            • located above basal layer
            • because it is above the basal layer the blister is weak
              • positive Nikolsky sign
                • outer epidermis separates with gentle rubbing
          • acantholysis
            • loss of connection between cells
          • post-inflammatory hyperpigmentation
        • treatment
          • immunosuppression (corticosteroids)
  • Hemidesmosomes
    • structure
      • composed of integrins
      • bind type IV collagen, fibronectin, laminin of basal lamina extracellularly
      • bind intermediate filaments intracellularly
    • function
      • like a desmosome but instead of attaching cell-to-cell it attaches cell-to-basement membrane
        • "half of a desmosome"
    • clinical importance
      • bullous pemphigoid 
        • pathophysiology
          • auto-IgG against basement membrane hemidesmosomes 
          • type II hypersensitivity
          • can be drug-induced
        • presentation
          • wide distribution of skin blisters
            • unlike pemphigus vulgaris → does not involve oral mucosae
            • vesicles below the epidermis
            • stronger vesicles
              • negative Nikolsky sign
          • NO acantholysis
        • treatment
          • immunosuppression (corticosteroids)
      • cancer
        • metastasis involves timely ↓ regulation of hemidesmosomal proteins
  • Gap junctions
    • structure
      • pores formed by 6 connexon proteins
    • function
      • allow direct passage of small molecules from one cell to another
        • e.g. Ca2+, cAMP
      • role in electrical and metabolic signalling
      • no role in strength 
 

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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