MTC Exam III part III Flashcards
microfilaments
actin polymers. help form microvilli. involved in cell shape, contraction, and intracellular trafficking
microtubules
made of tubulin and microtubule associated proteins. extend the length of the cell. important for mitotic spindle, cilia, flagella. major system of intracellular trafficking
What kind of change is likely to lyse a RBC?
a dramatic change in surface area
describe the “fishing net structure” of an RBC
short activin filaments and spectrin molecs are located below the plasma membrane
specrin is composed of triple alpha helical and beta subunits which associate in an antiparallel manner
they attach to ankynin complex, which attaches to band three (tm bicarb transporter)
spectrin als attaches to band 4.1R, which attaches to glycophorin C
describe vertical interactions in rbc structure
spectrin/ankynin/band 3 interactions; spectrin/actin/band 4.1R GPC interactions
hereditary spherocytes
cell shabe disorder with problems with vertical interactios of RBCs.
leads to spherical RBCs
autosomal dominant most of the time
less surface area
cells ge trapped in spleen
leads to hemolytic anemia, jaundice, and splenomegaly.
treatment: spleen removal (but probs with infection and iron/folate deficiency)
heterotypic vs. homotypic CAMs
cis vs. trans interactions
CAMs: integral membrane proteins that help cells adhere to each other
homotypic bind cells of same cell type; heterotypic bind cells of different cell types
cis binds cells on the same plane of the cell membrane; trans on different planes
4 types of junctions
anchoring junctions (structural integrity of tissues) occluding (prevent traffic thru intercellular space) channel-forming (enhance chemical and electrical coupling of cells) signal relaying: enhance cell-cell communication
classes of CAMs
cadherins, IG superfamily, integrins, selectins
cadherins. structure and types
E, N, and P. single pass TM. N terminal is extracellular, C terminal interacts with actin cytskeletion via alpha or beta catenin. require Ca2+
pemphigus vulgaris
autoimmune skin blistering from desmosomal cadherins
autoimmune response against desmoglein.
flaccid blisters
bullous pemphigoid
auto antibidies agasint hemidesmosomes which attach cells to the basal lamina
deeper, tensor leisons than pemphigus vulgaris
cell-matrix adhesion: outside in mechanism
ECM ligand biding causes integrin clustering. the active receptor conformation is straight out rather than folded. active form causes binding to a linker protein to the cytoskeleton
muscular dystrophy
DGC complex normally spans the muscle cell membrane and connects actin to the cell membrane. dystrogylcan and other protiens for the DGC complex. mutations in the DMD gene on X chromsome lead to less dystrophin which leads to weakness and muscle wasting. death and neuropsyche complications possible
convergent extension
change in cell packaging leads to movement
ameboid migration steps
extension, adhesion, translocation
describe how actin works wrt ameboid migration. include the proteins (2) that are critical for this process
globular actin is activated by ATP in nucleation process to form protofilaments
protofilaments bind to form d helical filaments
new actin is added to the plus side
ATP binds to the mins side
Arp2/3 complex and formins attach actin filaments to each other
Arp2/3 links the negative ends to the middle of other actin filaments to form a branched array
formins nucleate straight, unbranched filaments to each other.
ameboid extension
include the protein family and activation details
actin polymerization pushes a part of cell forward
rearrachement of the actin cytoskeleton under the control of Rho family monomeric GTPases. GTPases normally inactive but are activated by membrane bound guanine nucleotide exchange factors (GEFs). once activated, they help control Arp2/3 and formins
what proteins mediate the translocation step of ameboid migration?
myosin motors
Kti/Steel: what is this? for what cells is it important? what might we see in a heterozygote?
example of a survival factor/receptor pair needed for cell migration. found in germ cells, blood cells, neural crest cells. receptor is kit, survival factor is steel. kit heterozygotes have piedbaldism and possible mast cell leukemia, germ cell and GI tumors
describe the notch receptor structure and synthesis
single pass receptor. extracellular domains have lots of EGF-like repeats. synthesized in the golgi as a single peptide. then cleaved such that receptors are heterodimeric.
notch signaling pathway: what is the ligand? what happens upon binding?
DSL ligands found on nearby cells
when ligand binds, notch receptor undergoes two more cleavages. this releases an intracellular tail that goes toth the nucleus to bind a TF called CSL, which is a transcriptional activator (without tail, CSL actively inhibits notch targets)
alagille syndrome
JAG1 mutuation, which we thing is a DSL ligand
autosomal dominant
intraheptatic biliary hypoplasia leading to jaundice, cardiac probs, skeletal abnormalities/butterfly vertebrae, ocular abnormalities, facial abnormalities
CADASIL
cerebral arteriopathy, autusomal dominant subcortical infarts, leukoencepalpathy. notch 3 mutation.
TGF-beta receptors: type and structure
ser/thr kinases
2 types
type II homodimers bind ligands, then recruti, phosphorylate, and activate type I homodimers to for a heterotetramer
what happens upon ligand binding to TGF-b receptors
type II homodimers recurit and activate type I homodimers. together, they transduce they phosphorylate a smad. this smad associates with smad4. together, the smad complex goes to the nucleus and activates target genes
What Smads mediate TGF transcription vs BMP?
Smad 2 and 3 is TGF; Smad 1,5,8 is BMP
what are the 5 levels of TGF regulation
- TGF secreted into ECM in inactive form and not activated without help of throbospondin
- TGF antagonists exist
- so do inhibitory smads (smad6 and smad 7)
- co-receptors
- receptor decoys: bind the receptor but don’t trigger the pathway
HHT/Osler-Rendu-Weber syndrome
heretiary hemorrhagic telangiectasia
autosomal dominant
vascular dysplasia, lung, liver, and brain involvement with lots of bleeds
mutations in Eng, Alk1 or Smad4: probs with TGF-beta pathway
From what to arterio/venous malformations result in HHT? (4)
- loss of a/v identity in development
- abnormal vascular remodeling
- apoptosis of capillary epithelial cells
- dilation of anastamsoes because of loss of vascular smoolth muscle.
PAH: pulmonary artery hypertension
symptoms: SOB, increased R ventricular work and right ventricular failure
problem with TGF-B signaling with BMP, whish is neeaded for early vasculogenesis.
Marfan syndrome
affects ocular (myopia, displacement fof the lense, retinal detachment, glaucoma, cataracts), skeletal (bone overgrowth and jt laxity), and CV systems (aortic dilation and rupture, mitral valve prolapse, tricuspid valve prolapse). due to FBN1 mutations. caused by lack of fibrillin, which is needed in elastic and non-elastic tissues. And, FBN1 usually helps keep TGF-beta latent: FBN1 problems lead to over expression of TGFbeta signaling and excessive bone and aortic growth
loeys-dietz syndrome
similar to marfan syndrome but due to TGFbeta receptor issues (aortic aneurysi, arachnodactyly, etc.
from what are the limbs derived?
lateral plate mesoderm
Which T box genes are critical in the legs? In the arms?
Tbx 4 in legs and 5 in arms
describe proximal/distal limb growth orientaiton
controlled by AER (apical ectodermal ridge), which produces Fgfs 2,4, and 8.
progress zone is proximal to AER and consists of undifferentiated mesenchyme. the longer the time spent in the zone, the more distal the bone. Fgf4 expression maintained by Shh from the ZPA
describe dorsal/ventral specification of limb
dorsal identity determined by Wnt signalling pathway. Wnt indirect induces dorsal identity. ventral identity is the default (En1 signaling)
anterior/posterior specification in limb
anterior: thumb; posterior: pinky
controlled by zone of polarizing activity (ZPA) in the posterior region. ZPA confers posterior identity to limb cells using a Shh gradient
ZPA specified by Hoxb8 gene and regulated by retinoic acid. Shh expression maintained by Fgf4 form AER and vice versa.
Holt-Oram
TBX5 gene mutation leading to upper limb defects and congenital heart problems
GLI-3 defects
lead to brain and hand malformations
forebrain brain development: what determines anterior/posterior patterning?
Goosecoid from prechordal plate
brain devo: what determines dorsal/ventral patterning in the brain?
two opposing gradients: ventrally, it is Shh expression; dorsally, it is BMPs
together make a differential gradient
holoprosencephaly definition
single cerebral ventricle
SHH structure and synthesis
must be activated by an auto cleavage process. N-terminal signal seq is cleaved. the remaining peptide is cleaved into 2 halves by addition of acholesterol moiety to the C terminal of the half that was original the N terminal.
SHH signaling
SHH activated (requires cholestero). Shh goes to surface receptor PATCHED (aka PTCH) PATCHED releases Smo, which carries out a signaling cascade in the cell
general structure of a motile cilia
microtubule based organelle: 9+2 configuration
have hyneine and radial spokes
structure of a non-motile cilia
9+0 config with no dynein arms
What organelles are necessary for ciliogenesis? Where do they come from
basal bodies. can either come from mitosis or from generative complex/deuterosome
What two proteins are important for intraflagellar transport system?
kinesin2 brings molecules to the cilia tip and dyneine2 brings stuff back
how do motile cilia work?
sliding of the doublets against each other
there is an A and B tubule in each doublet. dyneine arms extend form A towards B (inner and outer), and radial spokes connected dynein arms around the central microbutule. sliding of doubles in a ATP dependent fashion occurs
Primary Cilia dyskinesia
autosomal recessive disorder characterized by chronic upper resp. infection and situs inversus
nodal vesicular parcel model vs. 2 cilia model
two models to explain how cilia are important in left/right determination
NVP: vesicles filled with Shh and retinoic acid are screted on the right side of the nod and are swept to the left via cilia. vesicles then open and cilia on the left of the node are chemical sensors
2 cilia model: motile cilia create a leftward flow sensed by left immotile cilia. cilia are mechanical sensors in this model.
what two senses require cilia?
smell and sight (rods and cones)
Bardet-Biedl syndrome
obesity, retinal rod/cone dystrophy, polydactyly, cog impairment, hypogonadism, UG malformation and nephropathy
genes are involved in IFT, esp. in parts of the brain that control hunger
Polycystic kidney diseases
autosomal dominant involving kidneys, liver, pancreas
primary cilia defects:
pallister-hall syndrome
autosomal dominant
hypothalamic probs, epiglottis, laryngeal cleft, pulmonary segmentation, polydacly
caused by GLI-3 problems. GLI3 mediates SHH pathway thru distal IFT
without SHH, GLIR represses SHH genes (retrograde transport of GLIR to cell body). with SHH, SMO is releases and transported to the tip such that GLIA predominates.
