0
SHUMEZ .H.
Introduction
 Keratins are a diverse group of structural proteins
that form the intermediate filament network
responsible...
 The expression of specific keratin genes is
regulated by the differentiation of epithelial cells
within the stratifying ...
 Most of the eukaryotic cells are composed of
cytoskeleton which is made of three components
microfilaments, intermediate...
Structure
 Each keratin is characterized by a chain of amino
acids as the primary structure, which varies in the
number a...
 Post translational modifications such as the
formation of disulphide bonds, phosphorylation
and glycosylation can influe...
The keratins are broadly divided into:
 Primary keratins are those keratins which are
always synthesized by the epithelia...
Based on distribution:
 Soft keratin: Found in the epidermis of skin in
the form of flattened non-nucleated scales that
s...
Based on X-ray diffraction pattern:
 Alpha : The X-ray diffraction pattern of this type
resembles that of α-helix . The α...
Based on amino acid sequence
 Type I family includes keratins numbered 9-20
which are composed of acidic proteins.
 Type...
Based on molecular weight:
 Low molecular weight keratins: Include keratins
with a molecular weight of 40kDa. These kerat...
Functions
 Keratins fundamentally influence the architecture
and mitotic activity of the epithelial cells.
 Keratins and...
 Keratins and its filaments are involved in cell
signalling, cell transport, cell compartmentalization
and cell different...
Factors regulating Differentiaition
 Growth factors like epidermal growth factor,
transforming growth factor alpha and be...
Effect of Retinoids on various keratins
Protein Effects
K1/10 Reduced expression
K13/19 Increased expression
K5, K16, K17 ...
Keratin distribution in epithelia
K5 / K14 Basal layer – keratinizined & non-
keratinized stratified epithelium
K1 / K10 K...
Keratinization disorders of skin
Defect Disorder
K5 / K14 Epidermolysis bullosa simplex
K1 / K10 Epidermolytic Icthyosis
K...
K8 & K18
 Keratins K8 & K18 are co-expressed and constitute
the primary keratin of simple epithelial cells.
 They are al...
K7 & K19
 They are the secondary or additional keratins of
simple epithelial cells.
 They are expressed notably in ducta...
 They are frequently co-expressed.
 Type I keratin K19 is the smallest keratin.
 They are used as tumour markers.
K20
 K20 is the simple epithelial keratin with most
restricted expression pattern.
 They are expressed in the gastric fo...
K5 & K14
 K5 & K14 form the primary keratin pair of
keratinocytes of stratified squamous epithelia,
including the epiderm...
 Ultrastructurally, K5/K14 keratin filaments are
bundled as tonofilaments and attached to
desmosomes and hemidesmosomes.
...
K15
 K15 keratin is a basal keratinocyte keratin and hair
follicle stem cell marker.
 In comparison to K5 and K14, K15 i...
K6 & K16
 These keratins are expressed in epidermis of
plantar glabrous skin, hair follicle outer root
sheath and compani...
K17
 K17 is a basal/myoepithelial cell keratin.
 It is expressed in myoepithelial cells of complex
tissues, including va...
 After skin injury, K17 is switched on in
regenerating and migrating epidermal keratinocytes
upon wound healing.
 K17 mu...
K1 & K10
 In the epidermis, the transition of keratinocytes
from basal cell layer to suprabasal spinous cell
layer is cha...
 Keratin filaments composed of K1/K10 pair form
particularly dense bundles which are so
characteristic of suprabasal epid...
 Mutations in K1 and K10 are associated with
blistering disorder – bullous congenital icthyosiform
erythroderma.
 Theref...
K9
 K9 is a highly specific keratin of terminally
differentiating keratinocytes of palmoplantar
epidermis.
 Mutations in...
K2
 Keratin specific for advanced terminal
differentiation process of epidermal keratinocytes.
 It is expressed in the u...
K3 & K12
 K3/ K12 are the keratin pair of the corneal
epithelium.
 They are expressed in all corneal epithelial cell
lay...
K4 & K13
 They are a highly characteristic keratin pair
indicating mucosal path of keratin differentiation.
 They are ex...
K76
 K76 is a highly specific keratin expressed in
suprabasal cell layers of oral masticatory
epithelium.
 They are foun...
K77
 Highly specific keratin restricted to the luminal
cells of eccrine sweat glands.
 Used as an eccrine duct marker.
Hair follicle specific keratins
 K25 - 28, K71 - 75
 These keratins are specifically expressed in the
companion layer, H...
Keratins of Hair Fiber
 K31 - 40, K81 - 86.
 These keartins are expressed within the cuticle
and the cortex of the hair ...
Keratins with unknown expression
 K23, K24, K78, K79, K80
 These five, very different keratins complete the
family of hu...
Types  of  keratin
Types  of  keratin
Types  of  keratin
Prochain SlideShare
Chargement dans... 5
×

Types of keratin

8,322

Published on

Published in: Technologies
0 commentaires
6 mentions J'aime
Statistiques
Remarques
  • Soyez le premier à commenter

Aucun téléchargement
Vues
Total des vues
8,322
Sur Slideshare
0
À partir des ajouts
0
Nombre d'ajouts
1
Actions
Partages
0
Téléchargements
203
Commentaires
0
J'aime
6
Ajouts 0
No embeds

No notes for slide

Transcript of "Types of keratin"

  1. 1. SHUMEZ .H.
  2. 2. Introduction  Keratins are a diverse group of structural proteins that form the intermediate filament network responsible for maintaining the structural integrity of keratinocytes.  There are around 30 families of keratin proteins divided into two groups namely acidic and basic which are arranged in pairs.  A total of 54 functional genes exist which codes for these keratin families.
  3. 3.  The expression of specific keratin genes is regulated by the differentiation of epithelial cells within the stratifying squamous epithelium.  Keratins and certain keratin associated proteins are useful as markers of differentiation because their expression is both region and differentiation specific.
  4. 4.  Most of the eukaryotic cells are composed of cytoskeleton which is made of three components microfilaments, intermediate filaments, and microtubules.  Among the various families and sub-families of intermediate filament proteins, keratin is an important type due to its high molecular diversity.
  5. 5. Structure  Each keratin is characterized by a chain of amino acids as the primary structure, which varies in the number and sequence of amino acid as well as in polarity, charge and size.  The amino acid sequence of a keratin influences the properties and function of the keratin filament.
  6. 6.  Post translational modifications such as the formation of disulphide bonds, phosphorylation and glycosylation can influence the conformation of the molecule and formation of keratin filaments.  Keratin filaments have a tripartite secondary structure consisting of an N-terminal head domain, a central α-helical rod domain and C- terminal tail domain.
  7. 7. The keratins are broadly divided into:  Primary keratins are those keratins which are always synthesized by the epithelial cells on a regular basis, e.g., K8/18 in simple epithelia, K5/14 in stratified epithelia.  Secondary keratins are those types of keratins which are produced by the epithelial cells in addition to or instead of primary keratins, e.g., K7/19 in simple epithelia, K15, and K6/16 in stratified epithelia. Classification
  8. 8. Based on distribution:  Soft keratin: Found in the epidermis of skin in the form of flattened non-nucleated scales that slough continually. The disulfide links are fewer in number which allows some stretching but returns to normal upon relaxation of tension.  Hard keratin: These are mainly found in nail, hair cortex, hair cuticle; the keratin type seen at these sites have very little flexibility owing to the presence of many cysteine disulfide crosslinks.
  9. 9. Based on X-ray diffraction pattern:  Alpha : The X-ray diffraction pattern of this type resembles that of α-helix . The α-helix is right handed and has 3.6 residues per turn. The hydrogen bonding occurs within one polypeptide chain.  Beta : The helix is right-handed with an average of 6 residues. The hydrogen bonding occurs between neighbouring polypeptide chains.
  10. 10. Based on amino acid sequence  Type I family includes keratins numbered 9-20 which are composed of acidic proteins.  Type II family includes keratins numbered 1-8 which are composed of basic proteins.
  11. 11. Based on molecular weight:  Low molecular weight keratins: Include keratins with a molecular weight of 40kDa. These keratins are mainly distributed in glandular and simple epithelia.  Intermediate molecular weight keratins: Include keratins with a molecular weight intermediate between 40kDa and 57kDa and are found in stratified epithelia.  High molecular weight keratins: Include keratins with a molecular weight of 57kDa and are seen in keratinized stratified epithelia.
  12. 12. Functions  Keratins fundamentally influence the architecture and mitotic activity of the epithelial cells.  Keratins and associated filaments provide a scaffold for epithelial cells and tissues to sustain mechanical stress, maintain their structural integrity, ensure mechanical resilience, to protect against variations in hydrostatic pressure and establish cell polarity.
  13. 13.  Keratins and its filaments are involved in cell signalling, cell transport, cell compartmentalization and cell differentiation.  Keratin filaments also influence cell metabolic processes by regulating protein synthesis and cell growth.  Keratins may also be involved in the transport of membrane bound vesicles in the cytoplasm of the epithelial cells.
  14. 14. Factors regulating Differentiaition  Growth factors like epidermal growth factor, transforming growth factor alpha and beta  Role of adjacent mesenchymal tissue  Components of extracellular matrix  Retinoids  Calcium
  15. 15. Effect of Retinoids on various keratins Protein Effects K1/10 Reduced expression K13/19 Increased expression K5, K16, K17 Slightly downregulated K4,K5, K14 Not affected Filaggrin Reduced expression Cornified cell envelope Suppressed Desmosomes Reduced in number
  16. 16. Keratin distribution in epithelia K5 / K14 Basal layer – keratinizined & non- keratinized stratified epithelium K1 / K10 Keratinized epidermis K6 / K16 Spinous layer - keratinized mucosa K4 / K13 Intermediate layer – non keratinized epithelium K19 Basal layer – non keratinized epithelium K9 Suprabasal layer – palmar & plantar epidermis
  17. 17. Keratinization disorders of skin Defect Disorder K5 / K14 Epidermolysis bullosa simplex K1 / K10 Epidermolytic Icthyosis K6 / K16, K17 Pachyonychia congenita K9 Epidermolytic palmoplantar keratoderma K1 Non-epidermolytic palmoplantar keratoderma K5 Epidermolysis bullosa with mottled pigmentation K4 / K13 White Sponge Nevus
  18. 18. K8 & K18  Keratins K8 & K18 are co-expressed and constitute the primary keratin of simple epithelial cells.  They are also the sole keratins of hepatocytes, acinar cells of pancreas and proximal tubular cells of kidney.  They are the first keratins to appear in embryogenesis.
  19. 19. K7 & K19  They are the secondary or additional keratins of simple epithelial cells.  They are expressed notably in ductal epithelia of small and large intestines, gastric foveolar epithelium, mesothelium, urothelium, as well as basal cells of non keratinizing stratified squamous epithelia.
  20. 20.  They are frequently co-expressed.  Type I keratin K19 is the smallest keratin.  They are used as tumour markers.
  21. 21. K20  K20 is the simple epithelial keratin with most restricted expression pattern.  They are expressed in the gastric foveolar epithelium, small and large intestinal epithelium, urothelium and merkel cells.  K20 positivity is predictive of a primary tumour in the gastrointestinal or pancreatobiliary tract.
  22. 22. K5 & K14  K5 & K14 form the primary keratin pair of keratinocytes of stratified squamous epithelia, including the epidermis and mucosal non keratinizing stratified squamous epithelia.  In the follicular outer root sheath they are uniformly expressed throughout all layers.
  23. 23.  Ultrastructurally, K5/K14 keratin filaments are bundled as tonofilaments and attached to desmosomes and hemidesmosomes.  Mutations of the K5 / K14 gene is responsible for the blistering disease – Epidermolysis bullosa simplex.
  24. 24. K15  K15 keratin is a basal keratinocyte keratin and hair follicle stem cell marker.  In comparison to K5 and K14, K15 is completely restricted to the basal cell layer of stratified squamous epithelia.  It is also expressed in the basal keratinocytes of the hair follicle bulge region.
  25. 25. K6 & K16  These keratins are expressed in epidermis of plantar glabrous skin, hair follicle outer root sheath and companion layer.  They are the constitutive components of nail epithelia.  Mutations in K6/K16 give rise to pachyonychia congenita type I.  These keratins are inducible upon stress, injury or inflammation.
  26. 26. K17  K17 is a basal/myoepithelial cell keratin.  It is expressed in myoepithelial cells of complex tissues, including various glands (sweat glands), respiratory epithelium and urothelium.  It is a prominent component of the suprabasal cell layers of outer follicular root sheath.
  27. 27.  After skin injury, K17 is switched on in regenerating and migrating epidermal keratinocytes upon wound healing.  K17 mutations have been identified in pachyonychia congenita type II and steatocystoma muliplex.  Like K6/K16, these keratins are also inducible upon stress, injury or inflammation.
  28. 28. K1 & K10  In the epidermis, the transition of keratinocytes from basal cell layer to suprabasal spinous cell layer is characterised by a profound change in keratin expression.  This involves a switch from expression of basal cell keratins ( K5, K14, K15 ) to suprabasal epidermal keratins, k1 and subsequently K10.
  29. 29.  Keratin filaments composed of K1/K10 pair form particularly dense bundles which are so characteristic of suprabasal epidermal keratinocytes.  This imparts mechanical integrity to the cells and the whole epidermis.  K10 specifically inhibits proliferation and cell cycle progression of keratinocytes.  Loss of K10 leads to increased keratinocyte turnover.
  30. 30.  Mutations in K1 and K10 are associated with blistering disorder – bullous congenital icthyosiform erythroderma.  Therefore, K1 and K10 are regarded as keratinization markers of keratinocytes.
  31. 31. K9  K9 is a highly specific keratin of terminally differentiating keratinocytes of palmoplantar epidermis.  Mutations in K9 gene are associated with skin disorder – epidermolytic palmoplantar keratoderma.
  32. 32. K2  Keratin specific for advanced terminal differentiation process of epidermal keratinocytes.  It is expressed in the uppermost epidermal layers - upper stratum spinosum, stratum granulosum.  Mutations in K2 are associated with icthyosis bullosa of Siemens.
  33. 33. K3 & K12  K3/ K12 are the keratin pair of the corneal epithelium.  They are expressed in all corneal epithelial cell layers.  Mutations in these keratins give rise to Meesmann’s corneal dystrophy.
  34. 34. K4 & K13  They are a highly characteristic keratin pair indicating mucosal path of keratin differentiation.  They are expressed in the entire suprabasal compartment of mucosal stratified squamous epithelia.  They are absent in the epidermis and adnexa.  Mutations in these keratins cause the disorder white sponge nevus of Cannon.
  35. 35. K76  K76 is a highly specific keratin expressed in suprabasal cell layers of oral masticatory epithelium.  They are found in the slightly orthokeratinized stratified squamous epithelium lining the gingiva and hard palate.
  36. 36. K77  Highly specific keratin restricted to the luminal cells of eccrine sweat glands.  Used as an eccrine duct marker.
  37. 37. Hair follicle specific keratins  K25 - 28, K71 - 75  These keratins are specifically expressed in the companion layer, Henle’s layer, Huxley’s layer and inner root sheath of the hair follicle.  Mutations in K75 predispose to the hair disorder pseudo-folliculitis barbae.
  38. 38. Keratins of Hair Fiber  K31 - 40, K81 - 86.  These keartins are expressed within the cuticle and the cortex of the hair follicle.  Mutations in some of these keratins leads to disorders like monilethrix and ectodermal dysplasia of hair and nail type.
  39. 39. Keratins with unknown expression  K23, K24, K78, K79, K80  These five, very different keratins complete the family of human keratin proteins.  But their expression patterns and functions are still unknown.
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×