PMID- 20406331
OWN - NLM
STAT- MEDLINE
DCOM- 20110120
LR  - 20240512
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 14
IP  - 7
DP  - 2010 Jul
TI  - Regulation of secretory granule size by the precise generation and fusion of unit 
      granules.
PG  - 1904-16
LID - 10.1111/j.1582-4934.2010.01071.x [doi]
AB  - Morphometric evidence derived from studies of mast cells, pancreatic acinar cells 
      and other cell types supports a model in which the post-Golgi processes that 
      generate mature secretory granules can be resolved into three steps: (1) fusion 
      of small, Golgi-derived progranules to produce immature secretory granules which 
      have a highly constrained volume; (2) transformation of such immature granules 
      into mature secretory granules, a process often associated with a reduction in 
      the maturing granule's volume, as well as changes in the appearance of its 
      content and (3) fusion of secretory granules of the smallest size, termed 'unit 
      granules', forming granules whose volumes are multiples of the unit granule's 
      volume. Mutations which perturb this process can cause significant pathology. For 
      example, Chediak-Higashi syndrome / lysosomal trafficking regulator (CHS)/(Lyst) 
      mutations result in giant secretory granules in a number of cell types in human 
      beings with the Chediak-Higashi syndrome and in 'beige' (Lyst(bg)/Lyst(bg)) mice. 
      Analysis of the secretory granules of mast cells and pancreatic acinar cells in 
      Lyst-deficient beige mice suggests that beige mouse secretory granules retain the 
      ability to fuse randomly with other secretory granules no matter what the size of 
      the fusion partners. By contrast, in normal mice, the pattern of granule-granule 
      fusion occurs exclusively by the addition of unit granules, either to each other 
      or to larger granules. The normal pattern of fusion is termed unit addition and 
      the fusion evident in cells with CHS/Lyst mutations is called random addition. 
      The proposed model of secretory granule formation has several implications. For 
      example, in neurosecretory cells, the secretion of small amounts of cargo in 
      granules constrained to a very narrow size increases the precision of the 
      information conveyed by secretion. By contrast, in pancreatic acinar cells and 
      mast cells, large granules composed of multiple unit granules permit the cells to 
      store large amounts of material without requiring the amount of membrane 
      necessary to package the same amount of cargo into small granules. In addition, 
      the formation of mature secretory granules that are multimers of unit granules 
      provides a mechanism for mixing in large granules the contents of unit granules 
      which differ in their content of cargo.
FAU - Hammel, Ilan
AU  - Hammel I
AD  - Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel 
      Aviv, Israel. ilanh@patholog.tau.ac.il
FAU - Lagunoff, David
AU  - Lagunoff D
FAU - Galli, Stephen J
AU  - Galli SJ
LA  - eng
GR  - R01 AI023990/AI/NIAID NIH HHS/United States
GR  - AI23990/AI/NIAID NIH HHS/United States
GR  - R01 CA072074-15/CA/NCI NIH HHS/United States
GR  - AI070813/AI/NIAID NIH HHS/United States
GR  - R01 CA072074/CA/NCI NIH HHS/United States
GR  - R01 AI070813-01/AI/NIAID NIH HHS/United States
GR  - CA72074/CA/NCI NIH HHS/United States
GR  - R37 AI023990/AI/NIAID NIH HHS/United States
GR  - R01 AI070813/AI/NIAID NIH HHS/United States
GR  - R01 AI023990-20/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20100419
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
SB  - IM
MH  - Animals
MH  - Cytoplasmic Granules/*physiology
MH  - Mice
MH  - Microscopy, Electron, Transmission
MH  - Mutation
PMC - PMC2909340
MID - NIHMS178830
EDAT- 2010/04/22 06:00
MHDA- 2011/01/21 06:00
PMCR- 2010/07/01
CRDT- 2010/04/22 06:00
PHST- 2010/04/22 06:00 [entrez]
PHST- 2010/04/22 06:00 [pubmed]
PHST- 2011/01/21 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - JCMM1071 [pii]
AID - 10.1111/j.1582-4934.2010.01071.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2010 Jul;14(7):1904-16. doi: 10.1111/j.1582-4934.2010.01071.x. 
      Epub 2010 Apr 19.