Talk:Pre-Medicine Program - Cell Export and Import

From CellBiology



Pancreatic function, type 2 diabetes, and metabolism in aging

Int J Endocrinol. 2012;2012:320482. Epub 2012 May 17.


Gong Z, Muzumdar RH. Source Department of Pediatrics, Divisions of Endocrinology and Geriatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Abstract

Aging is a risk factor for impaired glucose tolerance and diabetes. Of the reported 25.8 million Americans estimated to have diabetes, 26.9% are over the age of 65. In certain ethnic groups, the proportion is even higher; almost 1 in 3 older Hispanics and African Americans and 3 out of 4 Pima Indian elders have diabetes. As per the NHANES III (Third National Health and Nutrition Examination) survey, the percentage of physician-diagnosed diabetes increased from 3.9% in middle-aged adults (40-49 years) to 13.2% in elderly adults (≥75 years). The higher incidence of diabetes is especially alarming considering that diabetes in itself increases the risk for multiple other age-related diseases such as cancer, stroke, cardiovascular diseases, Parkinson's disease, and Alzheimer's disease (AD). In this review, we summarize the current evidence on how aging affects pancreatic β cell function, β cell mass, insulin secretion and insulin sensitivity. We also review the effects of aging on the relationship between insulin sensitivity and insulin secretion. Understanding the mechanisms that lead to impaired glucose homeostasis and T2D in the elderly will lead to development of novel treatments that will prevent or delay diabetes, substantially improve quality of life and ultimately increase overall life span.

PMID 22675349


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362843/figure/fig1/

Insulin degradation: progress and potential

Endocr Rev. 1998 Oct;19(5):608-24.

Duckworth WC, Bennett RG, Hamel FG. Source Veterans Affairs Medical Center, Omaha, Nebraska 68105, USA. Abstract Insulin degradation is a regulated process that plays a role in controlling insulin action by removing and inactivating the hormone. Abnormalities in insulin clearance and degradation are present in various pathological conditions including type 2 diabetes and obesity and may be important in producing clinical problems. The uptake, processing, and degradation of insulin by cells is a complex process with multiple intracellular pathways. Most evidence supports IDE as the primary degradative mechanism, but other systems (PDI, lysosomes, and other enzymes) undoubtedly contribute to insulin metabolism. Recent studies support a multifunctional role for IDE, as an intracellular binding, regulatory, and degradative protein. IDE increases proteasome and steroid hormone receptor activity, and this activation is reversed by insulin. This raises the possibility of a direct intracellular interaction of insulin with IDE that could modulate protein and fat metabolism. The recent findings would place intracellular insulin-IDE interaction into the insulin signal transduction pathway for mediating the intermediate effects of insulin on fat and protein turnover.

PMID 9793760


http://edrv.endojournals.org/content/19/5/608.long


[1]

Ribonucleic Acid (RNA)

  • 3 types of RNA
    • Messenger RNA (mRNA) translated into protein by action of ribosomes
    • Transfer RNA (tRNA) each tRNA is specific for a specific amino acid (anti-codon)
    • Ribosomal RNA (rRNA) Forms the backbone of ribosome subunits

(covered in other Pre-Medicine Biochemistry lectures)


Links: Messenger RNA movie | MCB - Overview of mRNA processing in eukaryotes | MCB - movie - Life Cycle of an mRNA


Abnormalities

Lysosomal Disorders

  • Several inherited disorders of lysosomal metabolism (OMIM Database 112 entries)
  • Tested at birth by Gutherie heel-prick
  • Lack of a specific enzyme, can isolate and measure enzyme activities

Danon disease

  • LAMP-2 (lysosomal associated membrane protein) deficiency in humans, fatal cardiomyopathy and myopathy (OMIM)

Mucopolysaccharidosis (MPS) IIIB (Sanfilippo Syndrome type B)

  • children develop disturbances of sleep, activity levels, coordination, vision, hearing, and mental functioning culminating in early death
  • deficiency in lysosomal enzyme N-acetyl-glucosaminidase (Naglu)

Peroxisome biogenesis disorders

(PBDs) Zellweger syndrome and neonatal adrenoleukodystrophy are fatal genetic diseases that are autosomal recessive.

History

Ribosomes first EM

Below are some example historical research finding related to exocytosis from the JCB Archive.

1955 Ribosomes, or the particles of Palade George Palade identifies particulate components of the cytoplasm, known initially as the particles of Palade and later as ribosomes.

1956 Microsomes are the in vitro ER George Palade and Philip Siekevitz unite the fields of microscopy and fractionation in this work. They conclude that Albert Claude’s biochemical fraction called microsomes are the in vitro version of the endoplasmic reticulum (ER) — a cytological feature first noted by Keith Porter.

1958 A pathway for secretion Radioactive proteins are followed after their synthesis as they progress towards their secretory fate; this allows the definition of not only trafficking pathways but of the organelles that lie along that pathway.

1966 Excess secretory products fuse with lysosomes Robert Smith and Marilyn Farquhar find that excess secretory granules are not stored but fuse with multivesicular bodies (MVBs) that then mature and fuse with lysosomes.

1975 Lost in translation: the signal hypothesis Günter Blobel and Bernhard Dobberstein use a Rube Goldberg concoction of mouse RNA, rabbit ribosomes, and dog ER to reconstruct cell biology's version of the ship in the bottle: how proteins a cell intends to secrete end up in the endoplasmic reticulum.

2009 The Nobel Prize in Chemistry 2009 awarded to Drs Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath "for studies of the structure and function of the ribosome".


References

Textbooks

Essential Cell Biology

  • Chapter 14 Intracellular Compartments and Transport

Molecular Biology of the Cell

Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002

Molecular Cell Biology

Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999


The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

Search Online Textbooks

Books

PubMed

  • PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed
  • PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC
  • Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM
  • Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez

Search Pubmed

Reviews

  • Lipid rafts and the regulation of exocytosis. Salaün C, James DJ, Chamberlain LH. Traffic. 2004 Apr;5(4):255-64. Review. PMID: 15030567

Articles

Vesicle association and exocytosis at ribbon and extraribbon sites in retinal bipolar cell presynaptic terminals. Zenisek D. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4922-7. Epub 2008 Mar 13. PMID: 18339810

A high-throughput screening of genes that encode proteins transported into the endoplasmic reticulum in mammalian cells. Ozawa T, Nishitani K, Sako Y, Umezawa Y. Nucleic Acids Res. 2005 Feb 24;33(4):e34.PMID: 15731327



References

Textbooks

Essential Cell Biology

  • Chapter 14 Intracellular Compartments and Transport, Endocytic Pathways p472

Molecular Biology of the Cell

Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002

Molecular Cell Biology

Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999

The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

Search Online Textbooks


Genes and Diseases

  • Genes and Disease selected range of human disorders by system.
  • OMIM Online Mendelian Inheritance in Man, an online database of genetic disorders and genes.

History

Below are some example historical research finding related to endocytosis from the JCB Archive.

1956 Catching sight of lysosomes Lysosomes are identified by Christian deDuve when a membrane barrier gradually dissolves, thus yielding the tell-tale release of an enzyme activity over time.

1964 Coated pits bring in the yolk A study of yolk protein uptake leads Thomas Roth and Keith Porter to propose that endocytosis is specific to a particular cargo and that the vesicle coat might be functioning in both selection and mechanical molding.

1967 How to make a lysosome Daniel Friend and Marilyn Farquhar find that transport pathways intersect: synthesized enzyme meets endocytosed protein in the lysosome.

1978 Viruses catch an endocytic ride into the cell Ari Helenius puts together snapshots of virus entry to form a coherent sequence of events.

Cell Structure Images

The linked pages below currently contain unlabeled electron micrographs showing specific cellular features.

header 1 header 2 header 3
Ribosomes_bound_mRNA_cartoon1
Mammalian proteins transported into er
Export from the ER in living cells
Post-Golgi_transport_cartoon
Golgi apparatus endocytic TGN
row 2, cell 3


Exocytosis and Endocytosis cartoon

Caveolae

Caveolae myoepithelial cells Caveolae

  • small membrane invaginations
  • defined by containing caveolin protein in the vesicle membrane
  • not always present in all cells
  • functions
    • lipid recycling
    • cellular signalling
    • endocytosis

Links: Parton RG, Simons K. The multiple faces of caveolae. Nat Rev Mol Cell Biol. 2007 Mar;8(3):185-94. Review. PMID: 17318224 FIGURE 3 Caveola endocytosis | Madame Curie Bioscience Database - Transmission electron micrographs of endothelial caveolae


Exosomes

  • nanometer-sized membrane vesicles invaginating from multivesicular bodies and secreted from different cell types
  • Function suggested as the eradication of obsolete proteins, antigen presentation, or "Trojan horses" for viruses or prions. (PMID: 16809645)

Endosomal Multivesicular Bodies (MVBs)/endosomes

  • a stage in endosomal development
  • A type of cytoplasmic vesicle (200 - 500 nmdiameter) that occurs when part of an endosome membrane invaginates and buds into its own lumen forming smaller contained vesicles.
  • smaller contained vesicles are degraded when the endosome fuses with a lysosome.
  • allows delivery of transmembrane proteins into the lumen of the lysosome for degradation.
  • compartments for receptor downregulation and as intermediates in the formation of secretory lysosomes. (PMID: 12892785)
  • delivery of transmembrane proteins into the lumen of the lysosome for degradation is mediated by the multivesicular body pathway. (PMID: 15569240)
    • The ESCRT (ESCRT-I, -II and -III) complexes form a network that recruits monoubiquitinated proteins and drives their internalization into lumenal vesicles within a type of endosome known as a multivesicular body. (PMID: 16689637)
  • essential for both sorting and multivesicular endosomes formation (PMID: 12892785)

Links: Biogenesis and function of multivesicular bodies. Piper RC, Katzmann DJ. Annu Rev Cell Dev Biol. 2007;23:519-47. Review. PMID: 17506697

Macropinosomes

  • Macropinocytosis defines a series of events initiated by extensive plasma membrane reorganization or ruffling to form an external macropinocytic structure that is then enclosed and internalized. The process is constitutive in some organisms and cell types but in others it is only pronounced after growth factor stimulation. Internalized macropinosomes share many features with phagosomes and both are distinguished from other forms of pinocytic vesicles by their large size, morphological heterogeneity and lack of coat structures. (PMID: 17760832)

Phagosomes

  • fusion of endoplasmic reticulum (ER) with macrophage plasmalemma, underneath phagocytic cups, is a source of membrane for phagosome formation in macrophages (PMID: 12151002)
  • phagocytic cup
    • actin-based membrane structure formed at the plasma membranes
    • impaired in Wiskott-Aldrich syndrome (WAS)