Part Bs (Epithelia, Differentiation, Bone and Skeletal muscle) Flashcards
Tight junctions
Claudins and occludins, create apical and basolateral sealing, selective barrier EG CLDN1 in Bowman’s capsule and restrict rotation around a junction
Adherens junctions
Ca2+ dependent cadherins - removed = less rigid, selective recognition (velcro) in homotypic cluster interactions (cardiac contraction) with alpha and beta catenins with recruited actin and myosin filaments
Experiment epithelia
N- E cadherin dependent cell sorting - that encode cell surface identity - heavy and light too - important in neural tube development and closing
Desmosomes
Mechanical strength dependent on desmogleins and desmocoilins, pemphigus is the result of ABs produced in response to these proteins
Gap junctions
Electrical and mechanical coupling - low resistance pathway 6 connexins make up one connexon - dextran tracer determines size - open/ close in response to diff things
Classification
Used to be according to visual - but now according to function as secretory, absorptive, protective or for transport
Actin Linked cell matrix
Anchors actin filaments to the ECM
Hemidesmosomes
Link intermediate filaments to the basal membrane in spot welding ( binding collagen and keratin filaments with an intermediate laminin - by alpha6beta8 integrin - identified by X-Ray crystallography
Thrombin internal signalling cascade result of active integrins
Epidermolysis bullosa
Genetic mutation of gene for keratin filaments COL7A1 gene is dystrophic bullosa - dermis and epidermis don’t link
Differentiation experiments
Demonstrate what is necessary and sufficient, determined from classical experimental biology (cutting and pasting) eg Transplantation of quail -chick chimera and neural crest cells, and ectopic graft of a dorsal limb onto a blastopore induces a secondary body axis and mice bred to be p53 deficient - Blackburn 2002
Morphenogenesis
Morphogenesis - form shaping process
Malformative has primary, deformative has secondary cause
3 layered embryo top down
Ecto, meso, endoderm
Signalling positions
Autocrine, juxtracrine, paracrine then endocrine
Wnt signalling
Binds to frizzled receptors plus LRP4 complex to degrade beta catenin - if not it accumulates and enters nucleus
Hedghog
SHH ligand binds to PTCH1 (TM protein) which activates SMO and int. signalling cascade to activate Gli TFs - dysregulated in cancer
TGFbeta
Ligand+ receptor + smad = activated transcriptional complex to target gene expression and act on -OH groups - defects in this cause PMDS - persistent Mullerian duct syndrome - internal female genitals and external male genitals
Tyrosine Kinase signalling
External PM receptor to ligand cases entry to nucleus and phosphorylation of a TF, faults = Pfeiffer syndrome (early fusion of certain bones) and Apert syndrome (FGFR2 and underdeveloped midfacial features)
Notch signalling
Physical interaction between signalling and receiving cell - used in binary lineage decisions for sc maintenence
Mutation in Jagged 1 notch 1 protein = Alagille syndrome and liver damage from too much bile build up
Osteoprogenitor cells
osteoblast and osteocyte precursors
Osteoblasts
Lay down new bone
Osteoclasts
Acidify and degrade bone
Osteocytes and recognition
Sclerostin (SOST gene - mutated is sclerosteosis) then activates osteoblasts and recruits osteoclasts - OBs then migrate to model in TF TGFbeta and osteoclasts activate in presence of RANKL and MCSF
Howships lacunae
Seal on damaged bone w/ ruffled border - H+ ions secreted from OCs by a proton pump then carbonic anhydrase produces more of these proteins, Cl- ions are exchanged for bicarbonate, HCl produced and degrades the bone, proteases then secreted, Ca2+ and signalling peptidases then released from broken down proteins and peptidases stimulate OB activation
OB activation
Stimulated by peptidases, osteocytes, hormones and PTH to release ODF (RANKL) and OPG to inhibit RANKL action by behaving as a decoy receptor = BALANCE
MSC to OPG
TF Runx2
Achondroplasia
FGF3 gene mutation promoted full chondrocyte differentiation = short long bones
TFG alpha
In presence of FGF stimulates MSCs to express T2 collagen and cells become chondroblasts for matrix formation
Mineralisation
Maturation of OBs to BLCs and then trapped in matrix network by canniliculi
Paget’s disease
The osteoclasts are larger than normal and break down bone faster than normal. The osteoblasts respond to this by depositing new bone at an increased rate
Ogen imperfecta
T1 collagen = weak bones
Osteoporosis
RankL and OPG imbalance
Rickets
Vit D3 deficient - Ca2+ deficience = weak bones
Hypercalcemia
Overactive osteoclasts = alters RMP and muscle spasms
Cross bridge cycle
Ca2+ dependent on the binding to troponin (TTNC) = conformational change on (TTNT) tropomyosin then. TTNI = Inhibitory subunit. Myosin heads bind to actin then ATP hydrolysis causes angle change from 90 to 45 degrees - breaks crossbridges - then ATPase on myosin head breaks down the new molecule of ATP bound to the myosin head which assists in the active transport of Ca2+ to the SR for the next AP to be received
Sarcomere
I band is actin only H band is myosin only, A band is overlap, Z line is boundary and M line is myosin
How is skeletal muscle innervated
ACh to nAChR on Sarcolamma
AP generation on skeletal muscle
Generated at sodium channel T4 subunit (SCN4A) which travels down the T tubules as the AP depolarises the dihydroxy receptor DHPR on the T tubules - this causes release of CA2+ from SR because of ionotropic change
Myasthenia gravis
IG antibodies are produced in response to nAChRs - and affects distribution of LRP4 and MuSK which control distribution of nAChRs (TM peptides)
Muscle contraction termination
Major is SERCA, small is the PMCa and the NCX
Regulation of active muscle tension
Selective recruitment (spatial summation) and frequency (temporal)
RYR1 disorder
Malignant hypothermia and problems w General anaesthetic - Ca2+ flood - RYR1 gene encodes the major sarcoplasmic reticulum calcium release channel of the skeletal muscle
Myosin myopathies
Problems w Force regulation - w Myosin binding protein C (cardiac type)
Nemaline myopathy
Faulty autosomal gene from each parent = bad tropomyosin
SKM structure
Muscle in epimysium to fascicle in perimysium to endomysium to myofibril in sarcolemma to actin/ myosin - all supported by ECM giving tensile strength
